LONG TERM FOLLOW UP OF THE HIGH RISK VLBW INFANTS Dr Pratibha - - PowerPoint PPT Presentation

LONG TERM FOLLOW UP OF THE HIGH RISK VLBW INFANTS

Dr Pratibha Agarwal Senior Consultant, Department of Child Development KK Women’s and Children’s Hospital, Singapore

The High Risk Infant – Challenges and Opportunities

• Challenge for ALL newborns to make the leap

from safe inutero to “hostile” exutero existence.

• Establish independent body function

– Thermoregulation – Cardiorespiratory – Cardiorespiratory – Metabolic

• Learning / Motor skills, feeding,

attachment and early communication cues.

High Risk Newborn

• Any newborn who has greater than average

chance of morbidity or mortality because of conditions superimposed on the normal course

• f birth events and postnatal adaptation.

Prenatal

• Low birth weight.
• Gestational age <28weeks.
• Intrauterine growth restriction

(IUGR).

• Male gender (♂).

Postnatal

• Neonatal seizures.
• Abnormal cranial ultrasound.
• Chronic lung disease (CLD).
• Infections.
• ECMO.
• ↓ Socioeconomic status
• Maternal depression

Classification of High Risk Newborns

• High Risk Newborn

According to size / Gestational Age

Gestational Age Gestational Age & Birth weight * Preterm (GA < 37 weeks) * SGA (Wt <10th centile)

• Term 38 – 42 weeks

AGA

• Post term > 42 weeks

LGA (Wt > 90th centile)

< 2500g – LBW < 1500g – VLBW < 1000g – ELBW ≥ 4 kg – Large

Prematurity stratification & incidence

Description Gestational age % of preterm birth

Extremely preterm < 28 weeks 6% Extremely preterm < 28 weeks 6% Very preterm 28 – 31 weeks 10% Moderately preterm 32 – 33 weeks 13% Late preterm 34 – 36 weeks 71%

High Risk Infants

• Hypothesis – Significantly less developed brain

structure & function (neurocognitive & behavioral) compared to controls.

• Poorer cognitive, behavioral & developmental
• utcomes hypothesised to be related to

– Lower grey & white matter volume – Poorer structural & functional connectivity (DTI & MRI) – Less mature metabolic profile (MRS)

High Risk Period

• Encompasses period of growth and viability upto 28 days following

birth… (upto 2 years)

Structure – volumes, gyration, sulcation. 13 weeks 30 weeks 36 weeks 6 months 2 years

Preterm Infants

• Period between preterm birth & term signifies the

beginning of the brain growth spurt & is potentially vulnerable to ex-utero environmental & nutritional influences.

Brain Brain

• ↑ Total Brain Volume – 22ml/wk
• Total grey matter - ↑ by 1.4% / week
• ↑ cortical grey matter volume
• No significant volume change in subcortical

grey matter (basal ganglia thalamus)

Ann Neurol 1998;224-235

“Programming”

“The concept that a stimulus or insult, when applied at a critical or sensitive period in early life , may have a long term or life-time effect on the structure

• r function of the organism”

(Lucas A 1991, Hales CN, Barker DJP2001)

Vulnerability vs Plasticity

Preterm Brain

Increased Vulnerability

• Rapidly growing tissues

– Exaggerated effect of insult

• Vascular instability
• Watershed areas (Periventricular areas)
• ↑ metabolic vulnerability in selective regions

(hippocampus)

Mid – Late gestational insult

• Alters frontal lobe development.
• Effect on cerebellar development
• Poorer executive function, planning &
• Poorer executive function, planning &

spatial memory.

• Caudate volumes significantly affected

by early nutrition & related to verbal IQ.

Neural Plasticity

Change in synaptic processess, neurogenesis & axon myelination Intrinsic capacity of brain for remodeling due to overproduction & trimming (blooming & pruning) of neuronal connections Allows developing synaptic architecture of brain to capture & incorporate experiences Co-ordination neural network activity Supports development & learning

Postnatal Period

• “Window of sensitivity” & reflect “Opportunity or

exposure” for interventions to exert their effect.

• Neural plasticity may mitigate effects of nutrient

deficiencies on brain by adapting / compensating. compensating.

• Experience in the NICU alters development.

– Postnatal nutrition, – Sensory overload / underload.

Pre-school years (1 – 5 years)

• Rapid & dramatic brain development
• Neural plasticity
• Fundamental of cognitive development

– Working memory – Attention – Attention – Inhibitory Control – Interpersonal skills – Language – Motor co-ordination

• Window of sensitivity

– Nutrient or non-nutrient intervention may cause region specific changes & postnatal neural development.

WHAT DO WE NEED WE NEED TO KNOW?

KK Women’s and Children’s Hospital

• Largest tertiary care perinatal centre in Singapore

(NICU– 37 beds, L2 – 60 beds).

• Annual delivery 13000 per year.
• VLBW – 200/year, ELBW – 90/year.
• Provide care to > 2/3 of ELBW infants in Singapore.
• In utero and outborn neonatal transfer

(local and regional)

Our Interest groups

• Very Preterm –VLBW < 32 weeks
• Late Preterm infants- 34-36 weeks
• Late Preterm infants- 34-36 weeks
• Term IUGR
• Breast Fed Infants

Implications of the Prematurity: As incidence increases, so does the cost

• Economic

– High risk obstetric & NICU care – Long term health & developmental concerns

• Societal
• Societal

– ↑ Cost in education & care – ↓ Productivity of parents

• Personal / Interpersonal

– Stress, Disruption – ↑ family demands

Survival

Neonatal survival in VLBW infants @ KKH

96% 59% 91% 50% 60% 70% 80% 90% 100%

(55%*) (88%*) (95%*)

27% 0% 10% 20% 30% 40% 50% < 500 501 - 750 751 - 1000 1000 - 1500 Survival

• n = 2105 Overall survival – 88%
• 2000 – 2010 (*) – NICHD data

Neonatal Mortality Rates according to Gestational Age

• OR (95%CI) of survival with high gestational age = 1.50 (1.29-1.74) p < 0.001
• OR (95%CI) of mortality with high gestational age = 0.82 (0.70-0.90) p = 0.022
• OR (95%CI) of comfort care with high gestational age = 0.21 (0.13-0.34) p < 0.001
• P values and OR(95%)CI were determined for difference according to gestational age with adjustment for birth weight; year and birth

BEYOND SURVIVAL…..

• How should patients and their families be counselled

about the morbidity associated with extremely preterm infants?

• Parents want to know whether their child will survive

+ ability to survive with/without a major disability

• Neonatal Morbidity
• Childhood Neurodevelopmental Outcome

Poor mental development Major NN morbidity ↑ Cerebral palsy

• Diplegia
• Hemiplegia

Visual Impairment / Blindness

BEYOND SURVIVAL NEONATAL MORBIDITY

Low motor development scores

• Quadriplegia

Blindness Major neonatal morbidities have an impact on later development & growth in childhood (IVH/CLD/NEC/Sepsis/ROP)

Neurocognitive outcome – Effects of neonatal morbidity

Neonatal morbidity % with disability No morbidity 18% 1 morbidity (BPD / IVH / ROP) 42% 2 morbidities 62% 3 morbidities 88%

Schmidt et al JAMA 2003:289;1124 - 1129

Neonatal Morbidity and Mortality in ELBW Infants KKH Data: 2000 - 2010

<500 (n=37) 501 – 750 (n=307) 751-1000 (n=502) 1001-1500 (n=1254) Total (n=2105) Survival 10 (27%) 178 (59%) 458 (91%) 96% 88% Sepsis 45% 45% 19% 6% 15% Severe IVH 21% 18% 9% 2.5% 6% Severe ROP in survivors 25% 44% 16% 0.7% 10% NEC 11% 11% 8% 4% 6% BPD in survivors 61% 58% 23% 4% 15%

Long Term Follow Up of the preterm NICU graduate

Neurodevelopmental outcome after preterm birth is the MOST IMPORTANT measure of NICU success!!!

Learning Objectives

• Discuss benefits of neonatal follow up program

for the NICU graduate.

• Define optimal ages of follow up assessment.
• Define challenges in long term
• Define challenges in long term

Follow up.

• Newer assessment needs

Questions to be Answered

• Survival of high risk neonates is improving?
• What lies beyond survival of NICU graduate ?
• Do LBW infants with normal IQ range, make

greater use of special education tools compared to full term peers ?

Questions to be Answered

• Quality of life is more important than mere

survival?

• Can they live independently & support

themselves?

• Do they develop normal social & family

relationships?

• What are long term metabolic &

cardiovascular implications?

Benefits of long term follow up

• 1. Early Detection of Developmental Disturbances

↓ Appropriate & adequate intervention & support ↓ Improved Outcome for Child & Family

• 2. Surveillance/Quality Improvement Tool (QI)
• To audit perinatal & neonatal practices
• Target neonatal morbidity associated with poor long

term outcome

• 3. Perinatal Counselling
• Antenatal counselling & development of guidelines for

resuscitation & care of infants at borderline viability

• 4. Research

Early Detection & Management of Medical & Developmental disturbances

• Infant & Family – Early Identification

Appropriate & Adequate Early intervention & support Improved Outcome Improve quality of care Involved physician

Risks of Disability in VLBW Infants

• Disability include

– None: 35% - 80% – Mild: 8% - 57% – Severe: 6% - 20% Mental Retardation 10% - 20% Cerebral Palsy 5% - 8% Blindness 2% - 11% Deafness 1% - 2% – Severe: 6% - 20%

Type of Disability

2yr Outcome

Cognitive Function - Classification Normal MDI > 85 Mild delay MDI 70 - 84 Significant delay MDI < 70 Neurodevelopmental Impairment (NDI) - Classification Mild Impairment MDI 70-84 Ambulant CP Severe Impairment MDI < 70 Non ambulant CP Deafness needing hearing aid Blind

DISABILITY Stratified by GA at 30 months (USA, SWEDEN, UK)

Reference – PATEL RM, Ann Journal Perinatal, 2016

KKH: Follow up data (in ELBW)

2 yr

• Follow up rate -85-90%
• Neurosensory impairment

CP – 10% Deafness – 2% Blindness – 2%

• Significant cognitive delay – 25%
• Severe disability – 25%

5 yr

• Follow up rate = 80%
• Improving psychometric scores at 5 yr
• Severe delay – 6%
• Special school – 10%

Agarwal P Ann Acad Med Singapore 2003; 32: 346 - 353

Limitations of 2 year assessment

• Unreliable - Transient nature of impairment of

motor and cognitive function at 2 years with catch up by early school age.

• Inadequate - Subtle cognitive difficulties,

behavioral and learning disorders with impact on academic achievement, not evident till school age.

Why Long Term Follow Up Of Cohort ?

• Follow up during the first 2 years of life
• presence of chronic illness
• handicaps - CP/Dev Delay - 10 - 20%
• Follow up to School Age
• ↑ frequency of developmental disturbances in preterm survivors -

formerly considered non-disabled formerly considered non-disabled

• Motor performance problems
• Visual & Auditory Impairments
• Cognitive & Behavioural problem
• School failure
• Special Education needs - 19 - 50%
• Diagnosis of learning disabilities, problem behaviour &

mild motor problems often delayed till school age

Agarwal P Ann Acad Med Singapore 2003; 32: 346 - 353

Timeline: Child Outcomes

Pediatrics 2004;114;1377-1397

The Usefulness of the Bayley II Psychometric Scores at 2 Years in Predicting Cognitive Impairment at 5 ½ years – Agarwal et al

Aims: To determine predictive value of 2 years Bayley scale of Infant Development II Mental Development Index (BSID II – MDI) for assessing cognitive function at 5 ½ years of age in ELBW survivors

Conclusions

• BSID – II MDI <70 is a poor predictor of cognitive
• utcome at 5 ½ years, especially in the absence of NSI.
• BSID II MDI >70 – very high negative predictive value at

5 ½ years.

• Univariate analysis Predictors of 5 years IQ < 70
• Birth weight, gestation, composite morbidity
• Lower family income, MDI2 < 70, Neurosensory impairment
• Regression analysis – Independent risk factors
• Neurosensory Impairment at 2 years
• Lower family income

Conundrum of Prediction

• Whether early cognitive scores improve, remain stable or

worsen over time is not yet clear.

• Early cognitive Developmental Scores – imprecise in

providing later outcome

• Low cognitive score in infancy indicate increased risk of

a problem, but lack specificity as to type of problem

• Low cognitive score in infancy indicate increased risk of

a problem, but lack specificity as to type of problem

• MDI <70 IQ<70

Possibly likelihood of problem

• Major case – related decisions at extremely low

gestational age should not be based solely on results of early cognitive assessment

• Long term data is critical

Neurodevelopmental Outcome in ELBW Infants

School Age

– Full scale IQ 90 (82-105) – Learning disability 25 – 40% – ↓ academic achievement 25 – 62% – ↓ academic achievement 25 – 62% – Grade repetition 15 – 34% – ADHD 33 – 37% – Behavioral concerns 25 – 50% – Anxiety disorders 8 – 14% – ↓ participation in sports 29% – High school graduate 50 – 75%

Stephens BE, PCNA 56 (2009; 631 – 646)

VLBW Follow Up Program in KKH

KKH – High Risk VLBW Follow up clinic

• Ongoing since 1990 (N1+N2)
• Structured program of neurodevelopmental and medical

follow up of VLBW babies

• Data collection & entry up to 8 years of life
• Psychometric assessment – 2, 5 ½ & 8 years
• Academic performance
• Learning disability

VLBW Follow Up Clinic Team

Strengths of KKH – VLBW Follow Up Program

• Structured established longitudinal program.
• Personalized follow up of individual patient & family

≥ 8 years by senior neonatologists.

• Dedicated, multidisciplinary team with expertise.
• Reliable large longitudinal data base for every

VLBW till 8 years (vs 30 month follow up – USA).

• Reliable and credible research output.

Fundamental goals of KKH – VLBW follow up programme in providing care to preterm NICU graduate

• Provide ongoing assessment of growth &

nutritional intake. nutritional intake.

• Deliver preventive care & appropriate medical

care.

• Periodically perform neurodevelopmental

assessments.

Goals of Initial Care – Follow up Clinics

• Enable meeting general healthcare needs
• Facilitate access to subspecialty care
• Facilitate access to subspecialty care
• Co-ordinate planning & communication of

therapies & care plans

Components of VLBW Follow Up Services

• Multidisciplinary approach

Neonatologist Psychologist Rehabilitative Services Ophthalmologist

Infant & Family

Rehabilitative Services PT / OT /SLT ENT Specialist MSW Dietician Others

• Neurology
• Paed surgeon
• GI /Respiratory

Growth & Nutrition assessment & Management Early Intervention KKH VLBW Preventive Care

• Immunization
• Anticipatory guidance

Family Support Financial Support Neurodevelopmental Assessment Management of reflux / BPD KKH VLBW Follow Up Clinic

Members Role 1) Neonatologist

• Coordinating central person
• Assess growth & screen for developmental

delay

Role of different personnel in KKH High Risk VLBW Follow up Programme

delay

• Management of medical issues &

intercurrent illness and anticipatory guidance. 2) PT / OT

• Assessment and grading of muscle tone and

power

• Plan an appropriate training program for

each infant with tone abnormalities

• To teach the parents for continuing the

prescribed exercises at home

Role of different personnel in KKH High Risk VLBW Follow up Programme

Members Role 3) Ophthalmologist

• Follow up of ROP screening
• Assessment of visual acuity & screening for

squint, refractory errors 4) ENT / Audiology

• Hearing assessment & management of

hearing impairment. 5) Dietician

• Nutritional advice regarding milk +

complementary feeds

• Management of FTT and special needs.

6) Psychologist

• For formal neurodevelopmental assessment
• Screening for behavioral problems and their

management

Members Role 7) MSW

• Key role: Providing support for family, ensure

compliance with follow up

Role of different personnel in KKH High Risk VLBW Follow up Programme

8) Subspecialties

• Neurologist – Seizures
• Gastroenterologist – GERD, Short Bowel

Syndrome

• Respiratory – Reactive Airway Disease,

Exacerbation of CLD.

Assessment Protocol

Tests 9 & 12 months 18 months 24 months 5 years 8 years Personnel Medical History & Physical Examination √ √ √ √ √ Doctor Developmental Screening ASQ 3 ASQ 3 ASQ 3 ASQ 3

• Doctor &

parents Screening parents Socio emotional ASQ SE ASQ SE ASQ SE ASQ SE ASQ SE Doctor & parents Motor / Visuo Motor PDMS PDMS

• VMI*

VMI* PT / OT Psychologist Behavior CHAT VABS ADHD* OT / Psychologist Psychometric / Cognitive

• BSID III

WPPSI – III PPVT - * WISC IV WRAT - III Psychologist

Research Questions

• Long term effects on cardiovascular & endocrine function

disorder.

• Impact of specific antenatal & neonatal interventions

(Magnesium sulfate, antenatal steroids, eg) on brain (Magnesium sulfate, antenatal steroids, eg) on brain growth & function?

• Determination of best screening tools for identification of

infants at risk of adverse neurodevelopment sequelae.

• Identify early surrogate markers for long term

neurodevelopment disability.

Expanding The Scope of High Risk Follow up

• To evaluate performance of VLBW children at

5 years old on executive functioning using:

– Behaviour Rating Inventory of Executive Functioning- Preschool Version (BRIEF-P) – Vanderbilt Attention Deficit/Hyperactivity Disorder

Aims and Purposes of the Study

– Vanderbilt Attention Deficit/Hyperactivity Disorder Parent Rating Scale (VADPRS) – Beery-Buktenica Developmental Test of Visual Motor Integration, 5th Ed (Beery VMI) – Bracken School Readiness Assessment (BSRA)

Future Directions

• National, regional and international

benchmarking is critical to improve neonatal care and outcome

• Research on population based cohort with
• Research on population based cohort with

standardized reporting of short term and long term outcome

• Improved assessment
• f learning disabilities

Thank You

• Parents of VLBWs will be approached and

invited to participate in the study with appropriate explanations provided.

Recruitment

appropriate explanations provided.

• Informed consent will be taken at the Child

Development Clinic during their outpatient visit.

• Cross-sectional study
• Very low birthweight (VLBW), <1251 g, born

between 2007 and 2008 children will be recruited

Methodology

for study. (N=140)

• Upon giving consent, the child will be assessed

by the research coordinator in addition to the routine assessments by the attending psychologist.

• Child will then be assessed by research coordinator

using the following:

– Behaviour Rating Inventory of Executive Functioning- Preschool Version (BRIEF-P) – Vanderbilt Attention Deficit/Hyperactivity Disorder- Parent Rating

Methodology

– Vanderbilt Attention Deficit/Hyperactivity Disorder- Parent Rating Scale (VADPRS)

• Routine clinical assessments will be performed on

the child by psychologist using the following:

– Bracken School Readiness Assessment (BRSA) – Beery-Buktenica Developmental Test of Visual Motor Integration, 5th Ed. (Beery VMI).

In the Pipeline

• Assessing executive function at age 5 ½ years.
• Assessing school readiness skills.
• Assessing health related quality of life.
• Assessing health related quality of life.
• Training of residents & trainees.
• Revising guidelines for

threshold of viability.

FINALLY

“The acid test for any society that claims to be civilized is whether it really protects the life & promotes the well being of its most life & promotes the well being of its most vulnerable citizens”

Van Des Maas (1997) - BMJ 315:73

Prematurity - Ongoing needs

• A. Respiratory
• Chronic lung disease
• Recurrent infection
• B. Nutritional
• Failure to thrive
• Failure to thrive
• Feeding issues
• C. Neurological
• Developmental delay
• Cerebral Palsy
• Mental Retardation
• Vision & Hearing Deficit

Surveillance

• Aims

– Establish a mechanism to systematically follow up & monitor care of high risk neonates, in hospital & post NICU discharge

• Benefits
• Benefits

– QI tool: Audit perinatal & neonatal NICU interventions – Monitor quality indicators for the NICU – Summarize information about centre outcomes for a specific condition (eg: NEC, CLD, ROP) – Influence health care policy to improve outcomes – Early detection of mild disabilities is important when prevention & not rehabilitation is the choice

Perinatal Counseling

• Centre specific outcomes for specific GA to

enable perinatal counselling & development

• f guidelines for resuscitation & care of

infants at borderline viability infants at borderline viability

Critical Period

• Phase in the life span during which an organism

has heightened sensitivity to exogenous stimuli that are compulsory for the development of a particular skill.

• Encompasses a relatively narrow time-frame

during which a particular brain region develops

• r a specific experience must occur.
• Eg: Well defined milestones –

neural tube closure at 22 days.

Sensitive Period

• More extended period of time during

development when an individual is more receptive to environmental stimuli, because of the sensitivity of the developing nervous system to specific stimuli. to specific stimuli.

Sensitive Period

• Periods of postnatal brain development.
• Flexible & broader time frame
• Eg: Visual & auditory cortex

– Formulation of experience dependent synapsis peaks at 4th postnatal months & gradual retraction until end of pre school period. – Binocular version – Critical period: 3 – 8 months – Sensitive period: up to 3 years.

Blindness / Severe Visual Impairment GA 26 – 27 weeks 1% - 2% ≤ 25 weeks 4% - 8% Refractory Errors – Myopia / Hyper metropia GA < 28 weeks 25% Prescription glasses GA 26 weeks vs term 24% vs 4% at 6 years

Neurosensory Outcomes

Prescription glasses GA 26 weeks vs term 24% vs 4% at 6 years Late Retinal Detachment ELBW teens 4.5% Hearing Aids GA < 26 weeks 5% – 6% Mild Hearing loss 4% Saigal S & Doyle LW The Lancet 2008;371:261-69

• Prognosis of very preterm infants changes substantially

with postnatal age

• Counselling of families should be repeated at intervals

5 YEAR OUTCOMES – 23 – 27 WEEKS

(Doyle L W – Paediatrics July 01)

• Counselling of families should be repeated at intervals
• Advice offered should vary with perinatal and postnatal

events

• In absence of adverse events, disability free outcome in

survivors was 93%

Neurodevelopmental outcome at age eight in geographic cohorts of children born at 22 – 27 weeks gestational age during the 1990s

Arch Dis Child Fetal Neonatal Ed 2010 Roberts G et al ;95:F90-F94

Combined mortality & morbidity

(Levene, 2004)

>90% ≥ 75% ≅ 60% < 40% < 50%

Conclusion

ELBW

• Higher incidence of impairment
• Higher incidence of learning disability & academic

problems in premies with normal IQ

• Complex mixture of multiple weaknesses

in neurospatial, visual motor & verbal abilities

Grunau et al 2002