EEGs for preterm infants: Predicting Long Term Outcomes part 3

In some parts of the world EEGs are frequently performed in very preterm infants in the first few days of life as a screening test, and occasionally used to redirect care if abnormalities are found. Is this justified?

Are there abnormalities which are visible shortly after birth which are good predictors of profoundly abnormal long term disabilities? Is there some other valuable reason for performing routine EEG in preterm infants? The literature here is fortunately not huge (at least fortunate for someone wanting to review it!) compared to some other issues.

If we search for inception cohort studies of EEG in the first week of life in defined groups  of at risk preterm infants, with good follow up rates and adequate description of outcomes, we find relatively few studies. (Now of course EEGs may be required for evaluation of certain clinical findings, particularly possible seizures, I am talking about routine EEG for prognostication here, I am also talking about traditional multi-channel EEG, there will be another post sometime about amplitude integrated EEG).

There are two main findings on EEG which have been evaluated, background patterns and sharp transients, particularly rolandic sharp waves.

Generally speaking, there does not seem to be much evidence that background patterns are very predictive of long term outcomes. Now the background EEG patterns of the preterm infants are discontinuous. Periods of quiescence are interspersed with bursts of activity. The duration of the periods of suppression can be quatified as the interburst interval, and several papers have proposed norms for the duration of the IBI and of the bursts; unfortunately the norms proposed vary widely from one publication to the next, for example at 25 weeks an IBI of more than 30 seconds, 45, 60 and 90 seconds have all been proposed as abnormal.

One relatively recent study by Le Bihannic  (Le Bihannic A, Beauvais K, Busnel A, de Barace C, Furby A: Prognostic value of EEG in very premature newborns. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012, 97(2):F106-F109 exemplifies some of the problems with this literature, they report EEG findings and outcomes of 61 infants of between 25 and 29 weeks gestation, 9 surviving infants from the same time period were not included. The follow up was of various durations and standardized testing was only done if the neurologist’s initial assessment found a problem (which I think is fine if you are only worried about serious long term consequences), there is no clear definition of severe or moderate impairment, except that the severely impaired children did not go to normal school, and moderate impairment included attention deficit, hyperactivity, and dyspraxia. The frequency of moderate and severe sequelae was well over 50%; 36, compared with 25 who were ‘normal’. The reported findings were that a dysmature EEG at some point during the hospitalisation had a reasonably good Positive Predictive Value for the combined outcome of severe or moderate sequelae. Now when moderately severe sequelae includes clumsiness (dyspraxia) I am not sure of the usefulness of this for clinical prediction, especially as the abnormalities on EEG were often only evident just prior to discharge at term equivalent age.

Another study from about 6 years ago, although with a relatively small sample of 32 preterm infants, also throws doubt onto the usefulness of term equivalent age EEG, (Randò T, Ricci D, Luciano R, Frisone M, Baranello G, Tonelli T, Pane M, Romagnoli C, Tortorolo G, Mercuri E et al: Prognostic value of EEG performed at term age in preterm infants. Child’s Nervous System 2006, 22(3):263-269.  background patterns at term were only weakly associated with long term problems. This paper notes some of the difficulties in interpreting the literature with previous studies describing with delayed maturation in the preterm EEG compared to term infants, equivalent maturation, or advanced maturation. 

Let us consider sharp transients on the other hand: temporal sharp transients are frequently seen in infants with all sort of major and minor problems including parenchymal injuries seen on ultrasound, they are only important it seems if they persist after the first week or so, and are numerous and high voltage. There is also some evidence that positive rolandic sharp waves, especially if of high voltage and frequent, are associated periventricular leukomlacia. With several studies suggesting they are very specific for PVL’, but the diagnosis of PVL is not always clearly defined, often persistent periventricular echodensity is included, which has a very poor inter-rater reliability. They are also said to be associated with the later development of abnormal motor function. But abnormal motor function in the largest series, from Marret and colleagues was a prospective cohort of 417 infants less than 33 weeks gestation who survived to be seen at 1 year (Marret S, Parain D, Menard JF, Blanc T, Devaux AM, Ensel P, et al. Prognostic value of neonatal electroencephalography in premature newborns less than 33 weeks of gestational age. Electroencephalography and Clinical Neurophysiology. 1997;102(3):178-85 Abnormal was described as either mild distal hypertonia or diplegia or tetraplegia at 12 months of age, and was seen in 108 infants. This is an extremely high incidence of PVL and of movement disorders in a relatively low risk population, making any external relevance questionable. Certainly the severity of some of these diagnoses must be questioned. There is also no evidence of a link between the rolandic sharp waves and cognitive outcomes.

Finally both PVL by these definitions and the rolandic sharp waves seem to be becoming less frequent, the paper by Le Bihannic noted above only found 2 EEGs with the finding.

One thing I haven’t discussed is seizures. Seizures are found occasionally in infants in these studies, and are usually associated with a poorer prognosis. Seizures are difficult to diagnose clinically in the preterm (and in the term infant) (Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Interobserver agreement in neonatal seizure identification. Epilepsia. 2009;50(9):2097-101. and are often under-diagnosed and mis-diagnosed.  More accurate diagnosis should lead to more appropriate treatment, and, one would hope, better outcomes (although that is not certain). So studies focused on seizure diagnosis and therapy have a potential to actually improve, rather than just attempt to predict, clinical outcomes.

So overall I don’t think there is enough evidence of accurate prediction of outcomes to warrant routine EEG monitoring of the preterm infant for that purpose, rolandic sharp waves if frequent (I didn’t go into it but there are 2 types and only type 1 seem important) may be highly predictive of PVL, but a confirmation of PVL with imaging would be required anyway, and they don’t correlate well with severity of outcome.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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