FollowUp of Newborns with IVH and PVL - The MetroHealth System

Follow-up of Newborns with 

IVH and PVL

Incidence of IVH/PVL 

• Declining IVH rates 

• Increasing PVL rates 

• Impact of changing survival rates 

• What is the denominator? 

• Ultrasound v. CT/MRI

IVH Incidence 

Declining secondary to ?- 

• Aggressive resuscitation, esp. for ELBW’s 

• Improved ventilation techniques 

• Exogenous surfactants 

• Prompt, cautious CV support 

• Aggressive OB management-c/s, steroids

• VLBW (

• Papile: 

Classification Systems 

Grade 1-subependymal germinal matrix 

Grade 2-IVH w/o ventricular dilatation 

Grade 3-IVH w/ ventricular dilatation 

Grade 4-additional parenchymal 

hemorrhage

Classification Systems 

• Levene: 

Grade 1-subependymal hemorrhage 

Grade 2-IVH in < 50% of lat. ventricles 

Grade 3-IVH in > 50% of lat. ventricles

CNS Development 

• Neurons- formed by completion of second 

trimester 

• Neuronal migration- accomplished by both 

passive migration and via radial glial 

‘guide’ 

- takes < 3 days early on 

- takes 1-3 weeks later in gestation


• Cerebral organization- neurons reach final 

destination, develop dendrites, axons, and 

connect to other neurons. 

• Astrocytes and oligodendroglia- ‘born’ 

during third trimester; form ‘skeletal’ 

framework of brain and produce myelin.


• Myelogenesis- lipid sheath formed from 

oligodendroglial contact to axon; allows 

higher velocity of electrical impulses. 

• Begins later in third trimester; very active at 

term; continues through adolescence; 

requires appropriate cell numbers and cell 

contacts; requires FA’s, PL’s, cholesterol, 

gangliosides-- so, nutritional status is 

important.


• Substantial evidence for specificity of 

inputs during sensitive periods of brain 

development to support normal cortical 

ontogenesis; Example-Amblyopia. 

• Concept of Plasticity-animal models.

• Confounders 

Outcome Issues 

-SES 

- Degree of medical illness 

- Birth weight 

- Gestational age 

- Other - cocaine

• Length of follow-up 

• ‘Lost’ patients 

Outcome Issues

Outcome Issues 

• Methods of follow-up 

• Testing modalities-are they comparable? 

• Physical exam?

• Controls 

- historical 

• Comparison Groups 

- peers 

-siblings 

Outcome Issues

• Length of follow-up 

• Size of study 

IVH Studies 

- hospital 

- regional 

-multi-center 

• Subset of ELBW/VLBW studies

IVH-Short Term Outcomes 

• Papile, New Mexico,1983 

•


• Sostek, Georgetown, 1987 

• Good prediction between 1 yr and 2 yr 

scores, but not from neonatal risk. 

• IVH constitutes only a limited, imperfect 

model of risk status. 

• Grade 1-2 IVH= No IVH


• Ross, Cornell, 1996 

• Grade 1-2’s worse on Piaget’s invisible 

location task (memory for location) v. 

preterm and full term controls at 2 yrs.


• Morales, 1987; Follow-up: ONE year 

• No IVH>Gr.1-2>Gr.3>Gr.4 on mental and 

motor scores, and neuro handicaps. 

• Mental: 96.5 (no IVH) v. 90.1(Gr.1-2) 

• Motor: 95.5(no IVH) v. 86.7(Gr. 1-2) 

• Neuro: 7%(no IVH) v. 11.5%(Gr.1-2)


• Vohr and Garcia Coll, Brown, 1989 

• Grade 3-4 (n=34) w/ worse mental and 

motor scores, worse eye-hand coordination, 

object manipulation, object relations (visual 

motor coordination) than preterm and full 

term controls at 2 yrs.


• Blackman, Iowa, 1991 

• 16 Grade 4 IVH’s ; follow-up-33 mo. 

-5/16, DQ>83 

- 9/16, DQ= 52-83 

-2/16, DQ


• Bendersky, Robert Wood Johnson,1995 

• 105 preterms; follow-up - 3 yrs. 

- Grade 3-4--worse in gross motor, 

receptive and expressive language. 

- Grade 1-2--no different than controls.


• Aziz, Alberta, 1995; Follow-up: 3 yrs. 

• 646 survivors, 500-1250 grams 

- Grade 2 IVH- 0/16 abnormal 

- Grade 3 IVH, IPE, +/or CV-29/63 (46%) 

abnormal. 

- Grade 4 IVH-12/14(86%) abnormal.


• Wilson-Costello, RB&C,1998 

•

IVH-Long Term Outcomes 

• Msall, Buffalo, 1991 

• 75 surviving 24-28 wks, 1983-84 cohort. 

- 19/75 w/ major impairments (9MR, 4CP, 

1 blind, 5 multiply handicapped). 

- 71/75-functionally independent 

- CP rel. risk= 5.8 for Grade 3-4 

- MR rel. risk=5.4 for hydoceph (not IVH)


• Vohr and Garcia Coll, Brown, 1992 

•


• Piecuch,UCSF, 1997-446 infants, 500-1000 

grams, 1979-91; follow-up-55 mo(+/- 33) 

- 61% normal survival 

- 59 w/ Gr.3-4 IVH or PVL 

- 22/59 (37%)-mod/severe neuro abnormal 

- 5/59 (9%)-mildly abnormal 

- 32/59 (54%)- normal


• Kilbride, U. of Missouri, 1998 

• 1983-85 and 1986-89,

IVH-Other Follow-up Issues 

• Christiansen, Little Rock, 1997 

•

IVH-Other Follow-up Issues 

• King and Cronin, Loyola-Chicago, 1993 

• 13 infants w/ Gr. 4 IVH and 11 GA and BW 

matched controls. 

- 12/13 IVH v. 8/11 controls w/ ocular 

abnormalities 

- 5/13 IVH v. 0/11 controls w/ visual loss 

(optic atrophy and ROP).

IVH-Hydrocephalus 

• Resch, 1996-299 IVH’s, 1984-1988 cohort 

• Follow-up: 5 yrs 

• 68 w/ hydrocephalus (23 died, 5 lost) 

10/40-normal 

10/40-mild neuro symptoms 

11/40-mod handicaps +/or mod MR 

9/40-severe handicaps +/or severe MR

• Associations: 

– Tocolysis 

– PDA 

– Hypotension 

– Hypocapnea 

– HFOV 

– Chorioamnionitis 

PVL 

– Early neonatal dexamethasone Rx

PVL-Etiology 

• Hypotension/ischemia 

• Impaired cerebral autoregulation 

• Oligodendroglial cell death due to free 

radical scavengers


• Final etiologic pathway: maturation- 

dependent vulnerability of oligodendroglial 

precursor cell, (major cellular target in 

PVL) 

– cells vulnerable to attack by free radicals, 

generated in abundance during ischemia - 

reperfusion.


• Chorioamnionitis associated w/ persistent 

inflammatory reaction at site of PVL 

• High expression of cytokines, especially 

TNFalpha and also interleukin - 1 beta


• Antenatal steroids - Protective ? 

(> 50% reduction)


• Cystic PVL (large v. small cysts) 

• Thinning PV white matter 

• Transient periventricular echodensities 

• Persistent periventricular echodensities 

• ‘Flares’

PVL-Echodensities 

• Bleeding into an ischemic area 

• Venous infarction

PVL Outcomes 

• deVries, Netherlands, 1993-504 infants,


• Ringelberg, Netherlands, 1993- 353 infants 

• Fazzi, Italy, 1994 


• 37 cPVL’s; follow-up, 5-7 yrs. 

- Small cysts: 2/11 w/ CP, 1/11 w/ MR, 7/11 

w/ mild neuro signs, 1/11 normal. 

- Large cysts:14/14 w/ CP. 

- Prolonged flare: 6/12 w/ CP, 4/12 w/ mild 

neuro signs, 2/12 normal.


• Rogers and Msall, Buffalo, 1994 

• 31 cPVL’s w/ 26 survivors; follow-up, 21.5 

mo, (range, 9-51 mo). 

- 26/26 w/ CP--54%quad,42%di,4% hemi. 

- 18/25 w/ MR 

- 14/14 quads w/ MR. 

- Bigger and more cysts seen w/ quad.


• Wilkinson, Australia, 1996 

• 12 severe cPVL’s; follow-up, 27.3 months. 

• 10/10 survivors w/ spastic quad and visual 

impairments.


• Rogers and Msall, Buffalo, 1998 

• 41 cPVL’s 

- 39/41 w/ CP 

- 18/41 w/ growth failure due to oral 

feeding impairment.


• Japan: Diplegia (72/81 PVL); Quadriplegia 

(12/45 PVL) 

• Japan: PVL most common etiology w/ 

spastic diplegia in premies 

• Italy: 30 preterm spastic diplegic, all w/ 

PVL


• Visual impairment prominent 

• Italy = 23/38 PVL’s w/ visual impairment 

(9 blind; 14 w/ low acuity) ; associated w/ 

decreased peritrigonal white matter 

• Italy: 21/29 PVL’s w/ some visual function 

abnormality; correlated highly w/ 

neurodevelopmental scores


• Sweden: 18 visually impaired children; 10 

w/ PVL affecting optic radiation per MRI 

• Sweden: 16/19 PVL’s w/ horizontal 

nystagmus; most w/ optic nerve hypoplasia 

• Netherlands: PVL most associated w/ 

visual-perceptual disabilities (no IVH 

association)

• Other associations: 


– West Syndrome (infantile spasms) 

– Schizophrenia

FollowUp of Newborns with IVH and PVL - The MetroHealth System

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