As I mentioned in the last post, the initial report of outcomes by Bassan and others showed that the infants with severity score 0, (unilateral haemorrhage without midline shift affecting one zone) had reasonably good outcomes, 7 of 8 had cognitive scores within the normal range, 4 of 8 were without gross motor dysfunction. They also showed that having a VP shunt did not change significantly the neurological or developmental outcomes. As should therefore be obvious ‘grade 4 hemorrhages’ with these characteristics should be considered relatively benign, warranting close follow-up, and surveillance for complications such as ventricular dilatation or development of multiple cysts. Many PVHI resolve with a single porencephalic cyst in their wake, some resolve and leave findings similar to cystic PVL, that second group may well have worse motor outcomes than single porencephalic cysts, I will come back to this point later.
The Bassan study reports is obviously very small numbers, there were only 30 infants with PVHI in all (which isn’t bad for such a relatively uncommon lesion), so I asked myself if there are other similar data with larger numbers.
The largest I have found so far is a study from North Carolina (Maitre NL, et al. Neurodevelopmental Outcome of Infants With Unilateral or Bilateral Periventricular Hemorrhagic Infarction. Pediatrics. 2009;124(6):e1153-60) which has outcome data from 69 surviving infants with PVHI, 52 unilateral and 17 bilateral. The infants with bilateral PVHI were more immature than the unilateral babies, otherwise there was little difference in the early clinical course of the infants, but their outcomes at up to 36 months were very different.
Infants with unilateral PVHI had a Bayley II MDI at 18 to 36 months which averaged 82, compared to 49 with bilateral PVHI (almost all had an assigned score of 49). Cerebral palsy was much less common and much less severe with unilateral than bilateral PVHI, 15 of the 17 with bilateral PVHI had moderate or severe CP, compared to 19 of the 52 with unilateral PVHI. In concert with these findings the proportion with BayleyII scores above -2 SD on the MDI was significantly better with unilateral PVHI. In this study there is no description or analysis of the extent of the lesion on each side, or the worse side. They did report that those infants who had PVL on late ultrasounds had worse MDI, worse PDI, and more severe motor dysfunction than those who had porencephalic cysts.
Van Buuren et al (van Buuren LM, et al. Cognitive outcome in childhood after unilateral perinatal brain injury. Developmental Medicine & Child Neurology. 2013;55(10):934-40)
reported the outcomes of 21 babies who had unilateral PVHI, it is a somewhat unusual cohort in that the mean gestational age was 30 weeks, and ranged from 26 up to 41 weeks. One strength of the study is the later age IQ testing (performed, however, between 6 and 20 years of age) which showed that the children who had PVHI had full-scale IQ results which were lower than the standardizing population, but mostly within one standard deviation of that population, with a mean of 86. Verbal IQ scores were not significantly different from the theoretical norm at 96. Infants with post-hemorrhagic ventricular dilatation did worse, with a mean IQ of 80 compared to a mean of 96 for those without. The extent of the lesions is not clearly described they are noted as being frontal, fronto-parietal, or parietal and that the location had no impact on outcome, they don’t mention laterality (uni- vs bilateral); 12 of the 21 had a hemiplegia, but the severity is not described.
A study from Groningen (Roze E, et al. Functional Outcome at School Age of Preterm Infants With Periventricular Hemorrhagic Infarction. Pediatrics. 2009;123(6):1493-500)
followed 21 babies who had PVHI, there were 38 babies with this diagnosis in the cohort, 15 died and 2 were not included in the follow-up. They showed that only a minority had significant functional impairments, even though 9 of them had bilateral PVHI, and 5 had extensive (described as fronto-parietal-occipital) lesions. Although 16 children had Cerebral Palsy, 13 were GMFCS 1 or 2, only 3 had more severe motor problems. Most of the cognitive outcomes were normal or mildly affected with only about 10% more than 2 SD below the standardized mean at 4.4 to 12 years of age. They did not show an association between bilateral or more extensive PVHI and worse outcomes, but clearly the power is relatively low for these comparisons. Post-hemorrhagic ventricular dilatation was present in 8 infants, who had poorer scores, again the numbers are very small, but they seemed to have more cognitive difficulties.
The ELGAN cohort study included 54 babies with a diagnosis of PVHI. (O’Shea TM, et al. Neonatal cranial ultrasound lesions and developmental delays at 2 years of age among extremely low gestational age children. Pediatrics. 2008;122(3):e662-9). 44% of them had a Bayley II MDI less than 70 at 2 years of age, and 59% had a PDI under 70, there is no analysis of whether unilateral or bilateral PVHI were different, to unilateral or localised lesions.
A more complex system called the Abdi score is calculated as the square of the highest traditional IVH grade (so scoring 1, 4, 9 or 16), plus the IVH grade on the contralateral side, plus 5 for each hemisphere when more than two of its territories are involved, and plus 5 when there is a midline shift of the brain. The “territories” refers to the brain regions from the Bassan system. The score was first published in the Saudi Medical Journal and I can’t access the paper to see how it was derived, but as far as I can tell it was rather arbitrary. A recent outcome study using the Abdi scores (Al-Mouqdad M, et al. A New IVH Scoring System Based on Laterality Enhances Prediction of Neurodevelopmental Outcomes at 3 Years Age in Premature Infants. American journal of perinatology. 2016(EFirst) followed 183 very preterm babies at 3 years of age. They included 55 babies with intraparenchymal bleeds, whose Abdi scores could range from 16 (i.e. 4-squared) to 35 (4-squared plus 4 plus 5 plus 5 plus 5). The authors showed that this score was better at predicting outcomes than simply using the Papile grade, but they did not compare to the Bassan system for PVHI. Although this score seems better for an individual patient prediction, it would be difficult I think to use it in daily practice, and the small numbers with each individual score mean that a very large database would be required to validate differences between each score
You may be asking yourself why is Keith Barrington/neonatalresearch.org going over all this older data? I was stimulated to do so by recent cases in my NICU and also by this publication from Texas (Sheehan JW, et al. Severe intraventricular hemorrhage and withdrawal of support in preterm infants. J Perinatol. 2017;37(4):441-7). The authors note that the long-term prognosis of very preterm infants with parenchymal hemorrhage has been shown to be much better than previously thought.
As you can hopefully see from this (non-exhaustive) review, the majority of infants with parenchymal bleeds (“grade 4 IVH” or PVHI) have outcomes which are within the range of healthy full term infants, only a minority have serious impairments (although, as most of the follow-up is only to 2 years of age, permanent functional impairments are impossible to quantify). As you might expect, but with little data to support it, it seems likely that more extensive hemorrhagic lesions, and bilateral lesions have worse outcomes than limited or unilateral lesions, but there are very few patients who are informative in the published cohorts.
Sheehan’s study examined discussions and decisions regarding redirection of care among very preterm infants with a diagnosis on ultrasound of serious brain injury (“grade 3 IVH” or PVHI). They showed that the improved knowledge about the benign outcome of many of these lesions has not led to fewer decisions for comfort care. They also examined the outcomes of survivors with PVHI: 13/35 or 37% had no or mild NDI, 10 or 29% had moderate-to-severe impairment and 12 or 34% had profound impairment. Survivors with profound impairment had a median of 4 (IQR 3, 4) territories vs 2 (IQR 2, 3) territories in survivors without profound impairment.
Their data are therefore quite consistent with others, that parenchymal injury is often compatible with little or no impairment, and that the more severe the parenchymal injury the more severe the disability (although with wide confidence intervals). But this has not led necessarily to changes in decision making.
Why is this? In any other area of medicine, I suggest, if outcomes were shown to be much better (or at least, much less bad) than previous beliefs about long-term outcomes, decision-making would surely have changed, no?
I think we should reconsider our outcome data, and how good we are at predicting profoundly adverse outcomes.
What I suggest is the follows:
- The construction of robust large databases which relate head ultrasound findings to long-term, functional, outcomes. With enough detail to be able to relate a particular constellation of findings to a range of probable outcomes. Such databases will need to take into account mortality, but that must be predicated on whether care was re-directed or not. Withdrawal of life-sustaining interventions as a result of head ultrasound (or other considerations of long-term outcomes) must be factored into such databases.
- Development of tools to teach neonatal and perinatal trainees (and established caregivers) how to counsel parents regarding the results which would be routinely available from 1.
We must move on from a discussion focussed on “your baby has a grade 4 hemorrhage” and “life therefore is no longer worth living” (often implying, or overtly saying, that the long-term outcome will be “terrible”). To “your baby has these findings on imaging” which means that she (or he) will most likely be within the following range of outcomes, the majority of which are associated with an entirely acceptable quality of life.