Neurodevelopmental outcome at 5.5 years in Dutch preterm infants born at 24-26 weeks' gestational age: the EPI-DAF study.

OBJECTIVE: After lowering the Dutch threshold for active treatment from 25 to 24 completed weeks' gestation, survival to discharge increased by 10% in extremely preterm live born infants. Now that this guideline has been implemented, an accurate description of neurodevelopmental outcome at school age is needed. DESIGN: Population-based cohort study. SETTING: All neonatal intensive care units in the Netherlands. PATIENTS: All infants born between 240/7 and 266/7 weeks' gestation who were 5.5 years' corrected age (CA) in 2018-2020 were included. MAIN OUTCOME MEASURES: Main outcome measure was neurodevelopmental outcome at 5.5 years. Neurodevelopmental outcome was a composite outcome defined as none, mild or moderate-to-severe impairment (further defined as neurodevelopmental impairment (NDI)), using corrected cognitive score (Wechsler Preschool and Primary Scale of Intelligence Scale-III-NL), neurological examination and neurosensory function. Additionally, motor score (Movement Assessment Battery for Children-2-NL) was assessed. All assessments were done as part of the nationwide, standardised follow-up programme. RESULTS: In the 3-year period, a total of 632 infants survived to 5.5 years' CA. Data were available for 484 infants (77%). At 5.5 years' CA, most cognitive and motor (sub)scales were significantly lower compared with the normative mean. Overall, 46% had no impairment, 36% had mild impairment and 18% had NDI. NDI-free survival was 30%, 49% and 67% in live born children at 24, 25 and 26 weeks' gestation, respectively (p<0.001). CONCLUSIONS: After lowering the threshold for supporting active treatment from 25 to 24 completed weeks' gestation, a considerable proportion of the surviving extremely preterm children did not have any impairment at 5.5 years' CA.

Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): a first-in-human, open-label intervention study.

BACKGROUND: Perinatal arterial ischaemic stroke (PAIS) is an important cause of neurodevelopmental disabilities. In this first-in-human study, we aimed to assess the feasibility and safety of intranasally delivered bone marrow-derived allogeneic mesenchymal stromal cells (MSCs) to treat PAIS in neonates. METHODS: In this open-label intervention study in collaboration with all neonatal intensive care units in the Netherlands, we included neonates born at full term (≥36 weeks of gestation) with MRI-confirmed PAIS in the middle cerebral artery region. All eligible patients were transferred to the neonatal intensive care unit of the Wilhelmina Children's Hospital. Neonates received one dose of 45-50 × 106 bone-marrow derived MSCs intranasally within 7 days of presenting signs of PAIS. The primary endpoints were acute and subacute safety outcomes, including vital signs, blood markers, and the occurrence of toxicity, adverse events, and serious adverse events. The occurrence of unexpected cerebral abnormalities by a repeat MRI at 3 months of age was a secondary endpoint. As part of standard clinical follow-up at Wilhelmina Children's Hospital, we assessed corticospinal tract development on MRI and performed motor assessments at 4 months of age. This study is registered with ClinicalTrials.gov, NCT03356821. FINDINGS: Between Feb 11, 2020, and April 29, 2021, ten neonates were enrolled in the study. Intranasal administration of MSCs was well tolerated in all ten neonates. No serious adverse events were observed. One adverse event was seen: a mild transient fever of 38°C without the need for clinical intervention. Blood inflammation markers (C-reactive protein, procalcitonin, and leukocyte count) were not significantly different pre-administration versus post-administration and, although thrombocyte levels increased (p=0·011), all were within the physiological range. Follow-up MRI scans did not show unexpected structural cerebral abnormalities. All ten patients had initial pre-Wallerian changes in the corticospinal tracts, but only four (40%) patients showed asymmetrical corticospinal tracts at follow-up MRI. Abnormal early motor assessment was found in three (30%) infants. INTERPRETATION: This first-in-human study demonstrates that intranasal bone marrow-derived MSC administration in neonates after PAIS is feasible and no serious adverse events were observed in patients followed up until 3 months of age. Future large-scale placebo-controlled studies are needed to determine the therapeutic effect of intranasal MSCs for PAIS. FUNDING: Netherlands Organization for Health Research and Development (ZonMw).

Two-year neurodevelopmental outcome in children born extremely preterm: the EPI-DAF study.

OBJECTIVE: In 2010, the Dutch practice regarding initiation of active treatment in extremely preterm infants was lowered from 25 completed weeks' to 24 completed weeks' gestation. The nationwide Extremely Preterm Infants - Dutch Analysis on Follow-up Study was set up to provide up-to-date data on neurodevelopmental outcome at 2 years' corrected age (CA) after this guideline change. Design: National cohort study. PATIENTS: All live born infants between 240/7 weeks' and 266/7 weeks' gestational age who were 2 years' CA in 2018-2020. MAIN OUTCOME MEASURE: Impairment at 2 years' CA, based on cognitive score (Bayley-III-NL), neurological examination and neurosensory function. RESULTS: 651 of 991 live born infants (66%) survived to 2 years' CA, with data available for 554 (85%). Overall, 62% had no impairment, 29% mild impairment and 9% moderate-to-severe impairment (further defined as neurodevelopmental impairment, NDI). The percentage of survivors with NDI was comparable for infants born at 24 weeks', 25 weeks' and 26 weeks' gestation. After multivariable analysis, severe brain injury and low maternal education were associated with higher odds on NDI. NDI-free survival was 48%, 67% and 75% in neonatal intensive care unit (NICU)-admitted infants at 24, 25 and 26 weeks' gestation, respectively. CONCLUSIONS: Lowering the threshold has not been accompanied by a large increase in moderate-to-severely impaired infants. Among live-born and NICU-admitted infants, an increase in NDI-free survival was observed from 24 weeks' to 26 weeks' gestation. This description of a national cohort with high follow-up rates gives an accurate description of the range of outcomes that may occur after extremely preterm birth.

Favorable parental perception of behaviour at two years' corrected age in very preterm-born children.

Problems in behavioural and emotional outcome are amongst the long-term sequelae of preterm birth. The exact prevalence and associations with perinatal risk factors are unknown. Minimal research has been performed in pre-school aged children, compared to school age. The primary aim of this study was to determine the prevalence of parent-reported behavioural and emotional problems at the age of two in children born at less than 30 weeks' gestational age and/or birth weight less than 1000 g. The secondary aim was to determine whether perinatal factors were associated with the behavioural and emotional outcome. Perinatal characteristics of 144 preterm-born children from the NeoLiFeS cohort were collected retrospectively. Of these children, 101 parents filled out a Childs Behaviour Checklist (CBCL) at the corrected age of two. The results of the CBCL tests were presented as Z-scores, a Z-score of 0 indicating the mean of behavioural scores in the norm population. A Z-score higher than zero indicates less behavioural problems than average, a negative Z-score indicates more problems. Associations between perinatal risk factors and CBCL-scores were analysed using linear regression analyses. Prevalences of clinically relevant CBCL scores were low, 4%, 2% and 5% for total score, internalizing score or externalizing score, respectively. Being part of a twin was associated with higher internalizing Z-scores, indicating less problems in emotional behaviour. Bronchopulmonary dysplasia was associated with lower Z-scores in total and externalizing behaviour. In conclusion, in our cohort generally very few problems in behavioural and emotional outcome were reported at the age of two.

A Parechovirus Type 3 Infection with a Presumed Intrauterine Onset: A Poor Neurodevelopmental Outcome.

Parechovirus type 3 (HPeV-3) infection is an important cause of illness in neonates. We present the first case of an infant with a HPeV-3 meningoencephalitis which presumably commenced in utero. Severe developmental delay was seen. In the case of inexplicable neonatal meningoencephalitis, an intrauterine onset of HPeV-3 infection might be the cause.

Outcome of Infants with Therapeutic Hypothermia after Perinatal Asphyxia and Early-Onset Sepsis.

BACKGROUND: Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis. OBJECTIVES: To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis. METHODS: In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.1-42.6 weeks and birth weight 2,280-5,240 g) with proven sepsis (n = 14) and probable sepsis (n = 28) was analyzed. Death, cerebral palsy, or a delayed development at 2 years was considered an adverse outcome. RESULTS: Sepsis was caused mostly by group B streptococci (n = 17), other Gram-positive bacteria (n = 5), and Candida albicans (n = 1). Of the 42 infants, 9 (21.4%) died, and 5 (11.9%) showed impairments on follow-up. The outcome is comparable to the previously reported outcome of infants with TH without early-onset sepsis. CONCLUSION: A good outcome was reported in the majority of infants with perinatal asphyxia, TH, and early-onset sepsis. Cooling should not be withheld from these infants.

The neurological phenotype of developmental motor patterns during early childhood.

INTRODUCTION: During early childhood, typical human motor behavior reveals a gradual transition from automatic motor patterns to acquired motor skills, by the continuous interplay between nature and nurture. During the wiring and shaping of the underlying motor networks, insight into the neurological phenotype of developmental motor patterns is incomplete. In healthy, typically developing children (0-3 years of age), we therefore aimed to investigate the neurological phenotype of developmental motor patterns. METHODS: In 32 healthy, typically developing children (0-3 years), we video-recorded spontaneous motor behavior, general movements (GMs), and standardized motor tasks. We classified the motor patterns by: (a) the traditional neurodevelopmental approach, by Gestalt perception and (b) the classical neurological approach, by the clinical phenotypic determination of movement disorder features. We associated outcomes by Cramer's V. RESULTS: Developmental motor patterns revealed (a) choreatic-like features (≤3 months; associated with fidgety GMs (r = 0.732) and startles (r = 0.687)), (b) myoclonic-like features (≤3 months; associated with fidgety GMs (r = 0.878) and startles (r = 0.808)), (c) dystonic-like features (0-3 years; associated with asymmetrical tonic neck reflex (r = 0.641) and voluntary movements (r = 0.517)), and (d) ataxic-like features (>3 months; associated with voluntary movements (r = 0.928)). CONCLUSIONS: In healthy infants and toddlers (0-3 years), typical developmental motor patterns reveal choreatic-, myoclonic-, dystonic- and ataxic-like features. The transient character of these neurological phenotypes is placed in perspective of the physiological shaping of the underlying motor centers. Neurological phenotypic insight into developmental motor patterns can contribute to adequate discrimination between ontogenetic and initiating pathological movement features and to adequate interpretation of therapeutic interactions.

Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. Lentiviral rescue experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex.

Perinatal Anemia is Associated with Neonatal and Neurodevelopmental Outcomes in Infants with Moderate to Severe Perinatal Asphyxia.

BACKGROUND: Perinatal anemia may cause perinatal asphyxia. Its pathophysiology and neurodevelopmental effects are theoretically different from other causes of perinatal asphyxia. OBJECTIVE: The study aimed to determine whether perinatal anemia results in different short-term and long-term outcomes than other causes of perinatal asphyxia treated with therapeutic hypothermia. METHODS: We retrospectively included infants with moderate to severe hypoxic-ischemic encephalopathy, born between May 2009 and October 2015. During follow-up, we assessed cognitive and motor development at 2-3 years of age, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Neurodevelopmental outcome (NDO) was classified as abnormal in case of cerebral palsy with Gross Motor Function Classification System ≥III and/or a BSID-III composite score < 85. Outcomes of infants with perinatal anemia (initial hemoglobin < 7 mmol/L) were compared to infants born with perinatal asphyxia due to other causes. RESULTS: In total, 111 infants were included of whom 30 infants (27%) died during the neonatal period. Infants with anemia (n = 23) had a higher mortality risk, OR 3.33, 95% CI 1.27-8.72, p = 0.01. None of the surviving infants with anemia (n = 12) had an abnormal NDO, in contrast to 26/69 (38%) with neurodevelopmental impairments, particularly motor problems, in the non-anemic group, p < 0.01. CONCLUSIONS: Perinatal anemia causing moderate to severe perinatal asphyxia is associated with a higher risk for neonatal mortality. All survivors with perinatal anemia, however, showed a normal NDO in contrast to children who were born asphyxiated due to other causes. The underlying pathophysiological mechanism for the favorable NDO in the perinatal anemia group needs further elucidation.

The Predictive Value of Amplitude-Integrated Electroencephalography in Preterm Infants for IQ and Other Neuropsychological Outcomes at Early School Age.

BACKGROUND: Amplitude-integrated electroencephalography (aEEG) is used increasingly in neonatal intensive care and seems helpful in predicting outcomes at the age of 2 years. OBJECTIVES: To determine whether early aEEG patterns in preterm infants are equally useful in predicting outcomes at early school age. METHODS: We recorded aEEG in 41 preterms (gestational age 26.0-32.9 weeks) at a median postnatal age of 9.7 h (IQR 7.0-25.3) and in 43 preterms on median day 8 (IQR 7-9). We assessed aEEG by pattern recognition and calculated the means of the aEEG amplitude centiles. At a median of 7.39 years, i.e., early school age, we assessed their motor, cognitive, and behavioral outcomes. RESULTS: Depressed aEEG patterns were not associated with poorer outcomes. Cyclicity directly after birth was associated with a higher total IQ (mean 104 vs. 97, p = 0.05) and higher scores on visual perception (mean percentile 57.1 vs. 40.1, p = 0.049) and visual memory (mean percentile 34.5 vs. 19.1, p = 0.090). We found some associations between the aEEG amplitude centiles and cognitive outcomes, but none for motor or behavioral outcomes. There was an increased risk of abnormal scores on long-term verbal memory in cases of the lower 5th and 50th aEEG amplitude centiles directly after birth. The odds ratios were 0.65 (95% CI 0.42-0.99, p = 0.040) and 0.71 (95% CI 0.52-0.96, p = 0.025), respectively. CONCLUSIONS: In relatively healthy preterm infants the value of aEEG in predicting neuropsychological outcomes at early school age is limited. The presence of cyclicity directly after birth tends to be associated with better cognition.

Amplitude-integrated electroencephalography during the first 72 h after birth in neonates diagnosed prenatally with congenital heart disease.

BackgroundLittle is known on amplitude-integrated electroencephalography (aEEG) during the first few days after birth in neonates with congenital heart disease (CHD). Our aim was, therefore, to assess electrocortical activity using aEEG within the first 72 h after birth in neonates diagnosed prenatally with CHD, and to define independent prenatal and postnatal predictors for abnormal aEEG.MethodsNeonates with CHD who were admitted to the neonatal intensive care unit between 2010 and 2017 were retrospectively included. We assessed aEEG background patterns, sleep-wake cycling, and epileptic activity during the first 72 h after birth and defined prenatal and postnatal clinical parameters associated with aEEG patterns.ResultsSeventy-two neonates were included. Twenty-six (36%) had mildly abnormal and six (8%) had severely abnormal aEEG background patterns at some point during the study period. Sleep-wake cycling was present in 97% of the neonates. Subclinical seizures were common (15%), whereas none of the neonates had clinical seizures. Only treatment with sedatives was a significant predictor for abnormal aEEG background patterns, explaining 56% of the variance.ConclusionAbnormal aEEG background patterns are common and are strongly associated with treatment with sedatives in neonates with prenatally diagnosed CHD. Future studies should assess the association between early postnatal aEEG abnormalities and neurodevelopmental outcome.

The prognostic value of proton magnetic resonance spectroscopy in term newborns treated with therapeutic hypothermia following asphyxia.

OBJECTIVE: The purpose of this study was to correlate brain metabolism assessed shortly after therapeutic hyperthermia by 1H magnetic resonance spectroscopy (MRS), with neurodevelopmental outcome. METHODS: At the age of 6.0±1.8days, brain metabolites of 35 term asphyxiated newborns, treated with therapeutic hypothermia, were quantified by multivoxel proton MRS of a volume cranial to the corpus callosum, containing both gray and white matter. At the age of 30months the Bayley Scale of Infant Development-III was performed. RESULTS: Infants that died had lower gray matter NAA levels than infants that survived (P=0.005). In surviving infants (28 of 35) there was a trend of negative correlation between gray matter choline levels and gross motor outcome (r=-0.45). In the white matter, choline correlated negatively with fine motor skills (r=-0.40), and creatine positively with gross motor skills (r=0.58, P=0.02). There was no relationship between lactate levels and outcome. CONCLUSION: MRS of asphyxiated neonates treated by therapeutic hypothermia can serve as predictor of outcome. Unlike previously reported associations in untreated asphyxiates, lactate levels had no relationship with outcome, which indicates that one of the working mechanisms of therapeutic hypothermia is reduction of the metabolic rate.

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.

Moderate unconjugated hyperbilirubinemia causes a transient but delayed suppression of amplitude-integrated electroencephalographic activity in preterm infants.

BACKGROUND: Unconjugated hyperbilirubinemia occurs frequently in preterm infants and may result in bilirubin encephalopathy. Amplitude-integrated electroencephalography (aEEG) is used to evaluate brain function in newborns. OBJECTIVES: To investigate the influence of total serum bilirubin (TSB) on the aEEG amplitude of preterm infants and to evaluate aEEG as a noninvasive method to identify acute bilirubin encephalopathy. METHODS: We performed a prospective observational study of 34 infants with a gestational age (GA) of 26-31 6/7 weeks. Infants had aEEG recordings on the 1st-5th, 8th and 15th day after birth. Infants with asphyxia, intraventricular hemorrhage >grade I or circulatory insufficiency were excluded. aEEG was evaluated by calculating the mean 5th, 50th and 95th centiles of the aEEG amplitudes. RESULTS: TSB peaked on the 4th day after birth. There was no synchronous relationship between TSB and aEEG amplitudes. The 5th, 50th, and 95th aEEG amplitude centiles on the 8th day correlated negatively with the TSB peak value (r = -0.37, p = 0.048; r = -0.60, p = 0.001; r = -0.44, p = 0.017, respectively), irrespective of GA. The 5th and 50th aEEG amplitude centiles increased with increasing GA (r = 0.45, p < 0.001, and r = 0.26, p < 0.001, respectively) and postnatal age (r = 0.25, p < 0.001, and r = 0.16, p = 0.023, respectively). CONCLUSIONS: TSB had no direct effect on aEEG amplitudes in preterm infants. There is, however, a delayed effect on electrocerebral activity in the 2nd week after birth.

The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia.

OBJECTIVE: Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. METHODS: A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. RESULTS: Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). CONCLUSION: In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. KEY POINTS: Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia. Choline and lactate levels in grey matter seem the best indicators of survival. Both grey and white matter should be examined during spectroscopy for perinatal asphyxia.

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.

Prenatal tobacco exposure influences cerebral oxygenation in preterm infants.

AIM: Our aim was to determine the influence of prenatal tobacco exposure on regional cerebral tissue oxygen saturation (r(c)SO(2)) and fractional tissue oxygen extraction (FTOE) in preterm infants. We hypothesized that as a result of vasoconstriction caused by prenatal tobacco exposure r(c)SO(2) would be lower and FTOE would be higher during the first days after birth in infants exposed to tobacco during pregnancy. METHODS: Sixty preterms were included in this prospective, observational cohort study (median gestational age 29.9 weeks, range 26.0-31.8, median birth weight 1248 g, range 615-2250). Fourteen infants had been exposed to tobacco during pregnancy. All mothers smoked more than five cigarettes a day till delivery. We measured r(c)SO(2) and transcutaneous arterial oxygen saturation (tcSaO(2)) in all infants on days 1-5, 8, and 15. FTOE was calculated: FTOE=(tcSaO(2)-r(c)SO(2))/tcSaO(2). RESULTS: In preterm infants exposed to tobacco during pregnancy, r(c)SO(2) was lower during days 1, 2, and 8 after birth, median 73% versus 81%, 73% versus 80% and 71% versus 78% respectively. FTOE was higher during days 1 and 8 after birth, median 0.24 versus 0.15 and 0.26 versus 0.19 respectively. On the second day, FTOE tended to be higher, 0.18 versus 0.14. CONCLUSIONS: During the first two days and day 8 after birth cerebral oxygen saturation is lower and oxygen extraction higher in preterm infants following prenatal tobacco exposure. Our data suggest that prenatal tobacco exposure may have an effect on cerebral oxygenation of the infant.

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.

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 (r(c)SO2), 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 r(c)SO2 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). R(c)SO2 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-r(c)SO2)/transcutaneous arterial oxygen saturation. RESULTS: Multilevel analyses showed that r(c)SO2 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 r(c)SO2 median 64% in infants with GMH-IVH versus 77% in control subjects and FTOE median 0.30 versus 0.17. R(c)SO2 and FTOE were not affected by the grade of GMH-IVH. CONCLUSIONS: Preterm infants with GMH-IVH had lower r(c)SO2 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.