Hendrik J. ter Horst

Prognostic significance of amplitude-integrated EEG during the first 72 hours after birth in severely asphyxiated neonates

Amplitude-integrated EEG (aEEG) is used to select patients for neuroprotective therapy after perinatal asphyxia because of its prognostic accuracy within several hours after birth. We aimed to determine the natural course of aEEG patterns during the first 72 h of life, in relation to neurologic outcome, in a group of severely asphyxiated term infants. Thirty infants, admitted to our neonatal intensive care unit from October 1998 until February 2001, were studied retrospectively. The aEEG traces obtained during the first 72 h after birth were assessed by pattern recognition: continuous normal voltage (CNV), discontinuous normal voltage (DNV), burst suppression (BS), continuous low voltage, and flat trace. Epileptic activity was also determined. The course of aEEG patterns was examined in relation to neurologic findings at 24 mo. Initially, 17 of 30 infants had severely abnormal aEEG patterns (BS or worse), which changed spontaneously to normal voltage patterns (CNV, DNV) in 7 within 48 h. The sooner the abnormalities on aEEG disappeared, the better the prognosis. The likelihood ratio of BS or worse for adverse outcome was 2.7 (95% confidence interval 1.4–5.0) between 0 and 6 h and increased to a highest value of 19 (95% confidence interval 2.8–128) between 24 and 36 h; after 48 h, it was not significant. Normal voltage patterns (CNV and DNV) up to 48 h of life were predictive for normal neurologic outcomes (negative likelihood ratios < 0.3). Our findings indicate that the course of aEEG patterns adds to the prognostic value of aEEG monitoring in asphyxiated infants. Spontaneous recovery of severely abnormal aEEG patterns is not uncommon.

Cerebral tissue oxygen saturation and extraction in preterm infants before and after blood transfusion

Objective Preterm infants often need red blood cell (RBC) transfusions. The aim of this study was to determine whether haemoglobin levels before transfusion were associated with regional cerebral tissue oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) and whether RBC transfusions were associated with rcSO2 and FTOE during the 24-h period thereafter. Design Prospective observational cohort study. Setting Third level neonatal intensive care unit. Patients Thirty-three preterm infants (gestational age 25–34 weeks, birth weight 605–2080 g) were included. Interventions None. Main Outcome Measures RcSO2 was measured during a 1-h period, before, 1 h after and 24 h after a 15 ml/kg RBC transfusion in 3 h. Using rcSO2 and transcutaneous arterial oxygen saturation (tcSaO2) values, FTOE was calculated: FTOE=(tcSaO2−rcSO2)/tcSaO2. Results Forty-seven RBC transfusions were given. RcSO2 and FTOE correlated strongly with haemoglobin before transfusion (r=0.414 and r=−0.462, respectively, p<0.005). TcSaO2 did not correlate with haemoglobin before transfusion. 24 h after transfusion, rcSO2 increased from a weighted mean of 61% to 72% and FTOE decreased from a weighted mean of 0.34 to 0.23. The decrease in FTOE was strongest in the group with haemoglobin below 6.0 mmol/l (97 g/l). The decrease in FTOE was already present 1 h after transfusion and remained unchanged at 24 h after transfusion. Conclusion Following RBC transfusion, cerebral tissue oxygen saturation increases and FTOE decreases. The data suggest that cerebral oxygenation in preterm infants may be at risk when haemoglobin decreases under 6 mmol/l (97 g/l).

Cerebral Oxygenation in Preterm Infants With Germinal Matrix-Intraventricular Hemorrhages

Background and Purpose— Preterm infants are at risk of developing germinal matrix hemorrhages–intraventricular hemorrhages (GMH-IVH). Disturbances in cerebral perfusion are associated with GMH-IVH. Regional cerebral tissue oxygen saturation (rcSO2), measured with near-infrared spectroscopy, and fractional tissue oxygen extraction (FTOE) were calculated to obtain an indication of cerebral perfusion. Our objective was to determine whether rcSO2 and FTOE were associated with GMH-IVH in preterm infants. Methods— This case–control study included 17 preterm infants with Grade I to III GMH-IVH or periventricular hemorrhagic infarction (median gestational age, 29.4 weeks; range, 25.4 to 31.9 weeks; birth weight, 1260 g; range, 850 to 1840 g). Seventeen preterm infants without GMH-IVH, matched for gestational age and birth weight, served as control subjects (gestational age, 29.9 weeks; range, 26.0 to 31.6 weeks; birth weight, 1310 g; range, 730 to 1975 g). RcSO2 and transcutaneous arterial oxygen saturation were measured during 2 hours on Days 1 to 5, 8, and 15 after birth. FTOE was calculated as FTOE=(transcutaneous arterial oxygen saturation−rcSO2)/transcutaneous arterial oxygen saturation. Results— Multilevel analyses showed that rcSO2 was lower and FTOE higher in infants with GMH-IVH on Days 1, 2, 3, 4, 5, 8, and 15. The largest difference occurred on Day 5 with rcSO2 median 64% in infants with GMH-IVH versus 77% in control subjects and FTOE median 0.30 versus 0.17. RcSO2 and FTOE were not affected by the grade of GMH-IVH. Conclusions— Preterm infants with GMH-IVH had lower rcSO2 and higher FTOE during the first 2 weeks after birth irrespective of the grade of GMH-IVH. This suggests that cerebral perfusion is decreased persistently for 2 weeks in infants with GMH-IVH, even in the presence of mild hemorrhages.

Cerebral oxygen saturation and extraction in preterm infants with transient periventricular echodensities.

OBJECTIVE: Our aim was to determine regional cerebral tissue oxygen saturation and fractional tissue oxygen extraction in preterm infants with transient periventricular echodensities. We hypothesized that as a result of reduced cerebral perfusion, regional cerebral tissue oxygen saturation will be lower and fractional tissue oxygen extraction will be higher during the first days after birth. PATIENTS AND METHODS: This was a prospective, observational study of 49 preterm infants (gestational age median: 30.1 weeks [26.0–31.8 weeks]; birth weight median: 1220 g [615–2250 g]). We defined transient periventricular echodensities as echodensities that persisted for >7 days. Regional cerebral tissue oxygen saturation was measured on days 1–5, 8, and 15 after birth. Fractional tissue oxygen extraction was calculated as (transcutaneous arterial oxygen saturation − regional cerebral tissue oxygen saturation)/transcutaneous arterial oxygen saturation. RESULTS: Transient periventricular echodensities were found in 25 of 49 infants. During the first week we found no difference between the 2 groups for cerebral tissue oxygen saturation and fractional tissue oxygen extraction values. On day 15 after birth, cerebral tissue oxygen saturation was lower in preterm infants with transient periventricular echodensities (66%) compared with infants without echodensities (76%) (P = .003). Fractional tissue oxygen extraction in infants with transient periventricular echodensities (0.30) was higher than fractional tissue oxygen extraction in infants without transient periventricular echodensities (0.20) (P < .001). The differences could not be explained by confounding variables. CONCLUSIONS: Persistent transient periventricular echodensities may be associated with increased cerebral oxygen demand after the first week after birth, which is contrary to our hypothesis. Cerebral oxygenation may be involved in the recovery of perinatal white matter damage.

Amplitude-integrated electroencephalographic activity is suppressed in preterm infants with high scores on illness severity

BACKGROUND The neonatal acute physiology score, SNAP-II, reflects the severity of illness in newborns. In term newborns, amplitude integrated EEG (aEEG), is depressed following asphyxia. In preterm infants aEEG is discontinuous, and therefore more difficult to assess compared to term infants. AIMS Our first aim was to investigate whether assessing aEEG amplitudes by calculating amplitude centiles was consistent with assessment by pattern recognition. Our second aim was to investigate whether the aEEGs of preterm infants were influenced by SNAP-II. STUDY DESIGN AND SUBJECTS We recorded aEEGs in 38 infants with a mean gestational age of 29.7 weeks (26.0-31.8 weeks) during the first five days of life. The mean recording time was 130 min. The aEEGs were assessed by pattern recognition, by calculating Burdjalov score, and by calculating the mean values of the 5th, 50th, and 95th centiles of the aEEG amplitudes. Illness severity was determined within the first 24h. RESULTS We assessed 151 recordings and found strong correlations between the 5th and 50th amplitude centiles and the Burdjalov scores (r=0.71, p<0.001 and r=0.47, p<0.001, respectively). The 5th and 50th amplitude centiles correlated with SNAP-II (r=-0.34, p<0.0001 and r=-0.27, p=0.001). These correlations were the strongest on the first day of life (r=-0.55, p=0.005 and r=-0.47, p=0.018, respectively). The 5th and the 50th amplitude centiles were best predicted by gestational age, SNAP-II, and low blood pressure. CONCLUSIONS Severe illness as measured by the SNAP-II, and low blood pressure had a negative influence on the aEEGs of preterm infants.

The Added Value of Simultaneous EEG and Amplitude-Integrated EEG Recordings in Three Newborn Infants

Amplitude-integrated electroencephalograms (aEEGs) recorded by cerebral function monitors (CFMs) are used increasingly to monitor the cerebral activity of newborn infants with encephalopathy. Recently, new CFM devices became available which also reveal the original EEG signals from the same leads. To date it was unclear whether this single-lead EEG provides additional information towards interpreting the aEEG traces more accurately. Our report deals with three cases in which the single-lead EEG from the CFM device did indeed reveal important additional information not provided by the aEEG alone. In cases 1 and 3, the aEEGs showed drifting of the baseline to higher amplitudes. The single-lead EEG revealed that this was due to muscle artefacts, high-frequency oscillation ventilation and the electrocardiogram rather than to cerebral activity. Hence, without knowledge of the EEG, the aEEG trace might have been misinterpreted as being fairly normal. Case 2 showed paroxysmal elevation of the lower margin of the amplitude on the aEEG which looked like epileptic activity. However, additional information from the single-lead EEG revealed that it was due to muscle artefacts. Thus, simultaneously recorded EEG can help to interpret seizure-like episodes on the aEEG. Conclusion: Simultaneously recorded single-lead EEGs can help to interpret aEEG traces more accurately.

Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period.

BACKGROUND Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). OBJECTIVE To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. DESIGN/METHODS We included 82 children (born 1998-2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP). RESULTS Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e., death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98-7.69; P=.055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42-32.82, P=.016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90-5.36; P<.001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99-32.97, P=.051. We found no association between seizure aetiology and outcome. CONCLUSIONS In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.

The relationship between electrocerebral activity and cerebral fractional tissue oxygen extraction in preterm infants.

Impaired cerebral oxygen delivery may cause cerebral damage in preterm infants. At lower levels of cerebral perfusion and oxygen concentration, electrocerebral activity is disturbed. The balance between cerebral oxygen delivery and oxygen use can be measured by near-infrared spectroscopy (NIRS), and electrocerebral activity can be measured by amplitude-integrated EEG (aEEG). Our aim was to determine the relationship between regional cerebral tissue oxygen saturation (rcSO2), fractional tissue oxygen extraction (FTOE), and aEEG. We recorded longitudinal digital aEEG and rcSO2 prospectively in 46 preterm infants (mean GA 29.5 wk, SD 1.7) for 2 hr on the 1st to 5th, 8th, and 15th d after birth. We excluded infants with germinal matrix hemorrhage exceeding grade I and recordings of infants receiving inotropes. FTOE was calculated using transcutaneous arterial oxygen saturation (tcSaO2) and rcSO2 values: (tcSaO2 − rcSO2)/tcSaO2. aEEG was assessed by calculating the mean values of the 5th, 50th, and 95th centiles of the aEEG amplitudes. The aEEG amplitude centiles changed with increasing GA. FTOE and aEEG amplitude centiles increased significantly with postnatal age. More mature electrocerebral activity was accompanied by increased FTOE. FTOE also increased with increasing postnatal age and decreasing Hb levels.

Traumatic Perforation of the Lamina Cribrosa During Nasal Intubation of a Preterm Infant

Traumatic perforation of the lamina cribrosa and penetration of the brain occurred during nasotracheal intubation of a preterm infant requiring resuscitation. This rare complication is specifically associated with the nasal route of intubation. The complication resulted in significant morbidity. The infant developed an extensive intracranial hemorrhage and posthemorrhagic hydrocephalus that required ventricular drainage. We recommend that nasotracheal intubation be performed with utmost care. We confirm Cameron and Lupton’s recommendation of using a small feeding tube over which to slide the endotracheal tube. Despite extensive iatrogenic damage, the patient’s neurodevelopmental follow-up at 2 years 9 months appeared relatively mild.

Early Erythropoietin for Preventing Red Blood Cell Transfusion in Preterm and/or Low Birth Weight Infants

Early administration of EPO reduces the use of RBC transfusions and the volume of RBCs transfused. These small reductions are of limited clinical importance. Donor exposure is probably not avoided since most studies included infants who had received RBC transfusions prior to trial entry. There was a significant increase in the rate of ROP (stage 3 or greater). Early EPO does not significantly decrease or increase any of the other important adverse outcomes. Ongoing research should deal with the issue of ROP and evaluate the current clinical practice that will limit donor exposure. Due to the limited benefits and the increased risk of ROP, early administration of EPO is not recommended. Evidence is lacking for the possible neuroprotective role of EPO in preterm infants.