Unilateral vs Bilateral Intraventricular Haemorrhage

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Intraventricular haemorrhage is associated with developmental delay and cerebral palsy. The likelihood of cerebral palsy & poor neurodevelopmental outcomes increases with IVH grade. But what if there’s only a bleed in one side?

 

Bottom Line:

IVH is bleeding into the ventricles.

IVH is more common in premature neonates.

Increasing Grade of IVH is associated with poorer neurodevelopment outcomes.

Bilateral Grade 4 IVH is associated with a poor prognosis, high rate of CP and low MDI & PDI scores.

Both Mehrer et al & Maitre et al found that infants with unilateral Grade 4 lesions had median cognitive scores that approach the mean for the general population, and better overall neurodevelopment outcomes.

Two recent articles looked at neurodevelopmental outcomes for neonates with unilateral or bilateral intraventricular haemorrhage. Here are my summaries;

Both papers looked at outcomes with respect to the laterality of the haemorrhage, for either all grades or grade 4 IVH. Firstly though, a brief background…

Intraventricular Haemorrhage (IVH) is bleeding in the ventricles, usually as a result of germinal matrix fragility from immature vessels, under stress. It is much more common in premature neonates: ~35% at 25 weeks gestation; ~18% at 29 weeks; and <10% at 31-32 weeks. In term neonates, severe IVH is rare. IVH is associated with poor neurodevelopment outcomes.

USS FindingOutcome
Normal5-8% have significant motor defect, IQ <70, moderate-severe disability
Grade 14-5% have severe disability
Grade 210-15% have severe disability
Grade 320-35% have CP / intellectual deficit / IQ<70
Grade 4~50-70% have CP / intellectual deficit / IQ<70 (30-60% will require VP shunt)
Grade 4 + cysts80% have moderate-severe disability, 90+%have CP

The first paper, by Maitre and colleagues, is Neurodevelopmental Outcome of Infants With Unilateral or Bilateral Periventricular Hemorrhagic Infarction (PVHI).

Who were the patients?

Patients were 69 infants with a birthweight <1500g. They had confirmed PVHI on early cranial USS,  and were born between 1998 and 2004.

Children were excluded for congenital viral infections, major CHD, genetic abnormalities, structural brain malformations, metabolic diseases & admission only for shunt insertion. 

PVHI is defined as IVH plus haemorrhagic necrosis of the periventricular white matter, which can occur with or without periventricular leukomalacia (PVL).

It’s the same as a Grade 4 IVH as per our earlier definition.

What did they look at?

Comparison: A comparison between those with unilateral and bilateral PVHI was undertaken, using Bayley Mental Developmental Index (MDI) scoring looking at motor and cognitive outcomes. Authors used binary outcome measures of MDI <70 or Psychomotor Developmental Index (PDI) <70. These were equivalent to 2SD below the population mean and correspond with significantly delayed development.

Were the groups similar?

Groups were relatively similar with the exception of a significantly lower gestational age for the bilateral PVHI group: unilateral (25.9wks) vs bilateral (24.6 weeks) (p=0.005).

What were the outcomes?

Outcomes: In models unadjusted for gestational age, outcomes appeared worse for bilateral PVHI; after adjustment the odds ratios were not substantially different.

Notably, for infants with bilateral PVHI, diplegic and quadriplegic cerebral palsy (CP) predominated. In infants with unilateral PVHI, CP was mostly hemiplegic.

Further subgroup analysis looked within the unilateral PVHI group to compare unilateral PVHI with or without PVL. The authors identified 2 distinct groups of infants with unilateral PVHI: one with cognitive indices that approached average scores, and the other with profound delays.

Patients without PVL appeared to have better outcomes; of those with unilateral PVHI, 78% of infants with PVL had moderate to severe CP versus 18% in the group without PVL. Those with PVL also had significantly higher rates of vision impairment and seizure disorders.

Infants with unilateral lesions had median cognitive scores that approach the mean for the general population.

Two thirds of infants with unilateral PVHI have CP, but in a majority of these infants, CP is mild. Conversely, almost all infants with bilateral PVHI have very poor cognitive and motor outcomes. 

This study was limited by the differences between gestation of unilateral & bilateral groups, and the retrospective nature. Despite the actual small numbers, this was one of the largest studies looking at this question.


The second paper is Mehrer‘s 2012 paper.

Grade and Laterality of Intraventricular Hemorrhage to Predict 18–22 Month Neurodevelopmental Outcomes in Extremely Low Birth Weight (ELBW) Infants.

Who were the patients?

Inclusion criteria was at least one abnormal cranial USS – including any grade IVH, ventricular dilatation, parenchymal cysts, cystic PVL or porencephalic cysts. The most severe cranial USS finding was used to categorise the infants. The authors did, however, exclude all periventricular leukomalacia in addition to lethal congenital abnormalities, chromosomal abnormalities and history of meningitis.

What did they look at?

Their study aimed to determine whether the laterality of IVH (unilateral versus bilateral) was a predictor of neurodevelopmental outcome at 18–22 months in a cohort of ~166 ELBW (<1000g) infants with Grades I– IV IVH.

This study is assessing the affect of laterality on outcomes for all Grades of IVH.

What were the outcomes?

The outcome measures were similar to Maitre’s study: cerebral palsy, PDI & MDI <70, however blindness and hearing impairment were added.

Unlike the Maitre study, regardless of statistical significance, laterality (unilateral vs. bilateral IVH) remained in the models, as it was directly related to the study hypothesis. This study had a bias towards the lower grades of IVH; their sample sizes reduced with increasing grade of IVH.

For Grade I-II, outcomes are unchanged between unilateral and bilateral IVH. There was a difference for MDI & PDI scores between unilateral and bilateral Grade 4 IVH, when controlled for a number of factors including sepsis, maternal steroids among others.

This quote from the Mehrer’s discussion nicely summarises their findings:

“[Maitre’s] findings are consistent with our study and suggest that the brain can adapt when there has been significant destruction of brain tissue on one side, but severe impairment usually results when there is parenchymal injury on both sides of the brain.”

The model is a multivariable logistic regression model, and there are clearly a number of confounders to be considered. The raw numbers of unilateral vs bilateral IVH at each grade are not stated – these could be quite small with respect to the conclusions drawn. In particular, I’d be interested to see the prevalence of a unilateral Grade 4 IVH without any contralateral haemorrhage, and whether the mechanisms are different to the remained of the population with IVH.


References:

—Maitre NL, Marshall DD, Price WA, Slaughter JC, O’Shea TM, Maxfield C, et al. Neurodevelopmental outcome of infants with unilateral or bilateral periventricular hemorrhagic infarction. Pediatrics. 2009; 124:e1153–60. [PubMed: 19948617]

——Mehrer SL, Tabangin ME, Meinzen-Derr J & Schibler KR. Grade and Laterality of Intraventricular Hemorrhage to Predict 18–22 Month Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants Acta Paediatr. 2012 April ; 101(4): 414–418

IVH, PVL and consequences. David W Cartwright, Director of Neonatology RBWH.  VOPP via iLearn@QHealth (Login Required)

Davies, Cartwright & Inglis. “Pocket notes on Neonatology 2E.” 2008.  Elsevier. (3rd Ed available as iPhone application)

Uptodate – “Clinical manifestations and diagnosis of intraventricular hemorrhage in the newborn”

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About 

A Paediatric Trainee based in Queensland, Australia, Henry is passionate about Adolescent Medicine & General Paediatrics, with a strong interest in Medical Education & Clinical Teaching. An admitted nerd & ironman with a penchant for Rubik's Cubes & 'Dad jokes'.

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