Boubou Hallberg

Spontaneous brain activity in the newborn brain during natural sleep--an fMRI study in infants born at full term.

Recent progress in functional neuroimaging research has provided the opportunity to probe at the brains intrinsic functional architecture. Synchronized spontaneous neuronal activity is present in the form of resting-state networks in the brain even in the absence of external stimuli. The objective of this study was to investigate the presence of resting-state networks in the unsedated infant brain born at full term. Using functional MRI, we investigated spontaneous low-frequency signal fluctuations in 19 healthy full-term infants. Resting-state functional MRI data acquired during natural sleep was analyzed using independent component analysis. We found five resting-state networks in the unsedated infant brain born at full term, encompassing sensory cortices, parietal and temporal areas, and the prefrontal cortex. In addition, we found evidence for a resting-state network that enclosed the bilateral basal ganglia.

Predictive value of fetal scalp blood lactate concentration and pH as markers of neurologic disability

OBJECTIVES We aimed to analyze the predictive value of the fetal scalp blood lactate concentration and pH, especially in regard to outcome variables that are strong predictors of impaired long-term outcome. An additional aim was to establish cutoff lactate levels in fetal scalp blood. STUDY DESIGN We conducted a retrospective study of all patients who had fetal scalp blood sampling performed because of an ominous fetal heart rate pattern at Huddinge University Hospital from October 1993 to October 1998. Fetal scalp blood sampling was performed in 1709 patients. The pH and the lactate concentration were determined in fetal scalp blood of 1221 and 814 of these patients, respectively. Outcome variables included pH <7.0 in umbilical artery blood; base deficit >16.0 mmol/L in umbilical artery blood; Apgar scores <7 at 1 minute, <7 at 5 minutes, and <4 at 5 minutes; and hypoxic-ischemic encephalopathy. RESULTS Sensitivity and specificity were generally higher in the lactate group than in the pH group, particularly in relation to an Apgar score <4 at 5 minutes and moderate to severe hypoxic-ischemic encephalopathy. In 326 patients the scalp blood lactate concentration and pH value had been obtained at the same time, thus allowing a comparison between these methods. The areas under the receiver operating characteristic curves were significantly higher for the lactate concentration than for the pH value with 2 outcome variables: Apgar score <4 at 5 minutes (P =.033) and moderate to severe hypoxic-ischemic encephalopathy (P =.015). CONCLUSIONS Our findings suggest that determination of the lactate concentration in fetal scalp blood is a more sensitive diagnostic tool than is determination of the pH value for predicting either an Apgar score <4 at 5 minutes or moderate to severe hypoxic-ischemic encephalopathy. In previous studies we also showed lactate measurements to be more often successful than pH analysis. Therefore we consider the measurement of lactate in fetal scalp blood to be an attractive alternative to pH analysis, and determination of the lactate concentration in fetal scalp blood seems to be a useful tool for monitoring the condition of the fetus. A suitable cutoff limit for fetal scalp blood lactate concentration as an indicator of fetal asphyxia could be 4.8 mmol/L.

Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO): an open-label, dose finding, and feasibility phase 1/2 trial

BACKGROUND Preclinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. METHODS In this open-label, dose finding, and feasibility phase 1/2 trial, we recruited full-term infants younger than 48 h who had hypoxic ischaemic encephalopathy and electrographic seizures not responding to a loading-dose of phenobarbital from eight neonatal intensive care units across Europe. Newborn babies were allocated to receive an additional dose of phenobarbital and one of four bumetanide dose levels by use of a bivariate Bayesian sequential dose-escalation design to assess safety and efficacy. We assessed adverse events, pharmacokinetics, and seizure burden during 48 h continuous electroencephalogram (EEG) monitoring. The primary efficacy endpoint was a reduction in electrographic seizure burden of more than 80% without the need for rescue antiepileptic drugs in more than 50% of infants. The trial is registered with ClinicalTrials.gov, number NCT01434225. FINDINGS Between Sept 1, 2011, and Sept 28, 2013, we screened 30 infants who had electrographic seizures due to hypoxic ischaemic encephalopathy. 14 of these infants (10 boys) were included in the study (dose allocation: 0·05 mg/kg, n=4; 0·1 mg/kg, n=3; 0·2 mg/kg, n=6; 0·3 mg/kg, n=1). All babies received at least one dose of bumetanide with the second dose of phenobarbital; three were withdrawn for reasons unrelated to bumetanide, and one because of dehydration. All but one infant also received aminoglycosides. Five infants met EEG criteria for seizure reduction (one on 0·05 mg/kg, one on 0·1 mg/kg and three on 0·2 mg/kg), and only two did not need rescue antiepileptic drugs (ie, met rescue criteria; one on 0·05 mg/kg and one on 0·3 mg/kg). We recorded no short-term dose-limiting toxic effects, but three of 11 surviving infants had hearing impairment confirmed on auditory testing between 17 and 108 days of age. The most common non-serious adverse reactions were moderate dehydration in one, mild hypotension in seven, and mild to moderate electrolyte disturbances in 12 infants. The trial was stopped early because of serious adverse reactions and limited evidence for seizure reduction. INTERPRETATION Our findings suggest that bumetanide as an add-on to phenobarbital does not improve seizure control in newborn infants who have hypoxic ischaemic encephalopathy and might increase the risk of hearing loss, highlighting the risks associated with the off-label use of drugs in newborn infants before safety assessment in controlled trials. FUNDING European Communitys Seventh Framework Programme.

The prognostic value of early aEEG in asphyxiated infants undergoing systemic hypothermia treatment.

Background:  Induced moderate hypothermia (HT) for 72 h has been shown to reduce the combined outcome of death or severe neurodevelopmental disabilities in asphyxiated full‐term infants. A pathological amplitude integrated EEG background as early as 3–6 h after birth, has been shown to correlate to poor prognosis.

Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants

OBJECTIVE To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96±9.5 for the cognitive scale, 97±14 for language scales, and 103±15 for motor scales, all within the normal range for age. Compared with the term-born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome.

Passive induction of hypothermia during transport of asphyxiated infants : a risk of excessive cooling

Background: Induced mild hypothermia is an emerging therapy that has been shown to reduce the combined outcome of death or severe neurodevelopmental disabilities in asphyxiated full‐term infants if started within 6 h after birth.

White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study

Aim:  To investigate cerebral white matter (WM) abnormalities (J Pediatr 2003; 143: 171) and diffuse and excessive high signal intensities (DEHSI), (J Pediatr 1999; 135: 351) in a cohort of extremely preterm infants born in Stockholm during a 3‐year period, using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).

Moderate neonatal encephalopathy: Pre- and perinatal risk factors and long-term outcome

Background. The aim was to describe pre‐ and perinatal data and long‐term neurodevelopmental outcome (15–19 years) in children born at term with Apgar score <7 at 5 min and moderate neonatal encephalopathy. Methods. The study is based on a population‐based birth‐cohort of children born in Sweden in 1985. Maternal, delivery, neonatal, and neuropaediatric data were compiled. Neurodevelopmental status was classified according to the presence of 1. cerebral palsy or other major impairments, 2. exclusively cognitive impairments, and 3. no impairments. Results. The majority of the children (81%) had cognitive dysfunctions, with or without other impairments, such as cerebral palsy. The rates of post‐term birth (19% versus 8%) and breech presentation (12% versus 3%) were significantly higher than in the general Swedish population. Pre‐ and perinatal data did not differ notably between the three outcome groups. Questionable or suboptimal obstetric care was common (55%). Conclusions. The study shows that children born at term with moderate neonatal encephalopathy have a high rate of cognitive dysfunctions with or without cerebral palsy at long‐term follow‐up. Our pre‐ and perinatal data did not correlate with outcome.

Brain abnormalities in extremely low gestational age infants: a Swedish population based MRI study

Aims: Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors.

Cranial ultrasound and MRI at term age in extremely preterm infants

Objectives Conventional MRI at term age has been reported to be superior to cranial ultrasound (cUS) in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in a previous study cUS was performed during the first 6 weeks only and not in parallel to MRI at term age. Therefore, the aim of the present work was to study brain injuries in preterm infants performing concomitant cUS and MRI at full-term age. Methods In a population-based cohort of 72 extremely low gestational age infants paired cUS and conventional MRI were performed at term age. Abnormalities on MRI were graded according to a previously published scoring system. On cUS images the lateral ventricles, the corpus callosum, the interhemispheric fissure and the subarachnoidal spaces were measured and the presence of cysts, grey matter abnormalities and gyral folding were scored. Results Moderate or severe WM abnormalities were detected on MRI in 17% of infants and abnormalities of the grey matter in 11% of infants. Among infants with normal ultrasound (n=28, 39%) none had moderate or severe WM abnormalities or abnormal grey matter on MRI. All infants with severe abnormalities (n=3, 4%) were identified as severe on MRI and cUS. Conclusions All severe WM abnormalities identified on MRI at term age were also detected by cUS at term, providing the examinations were performed on the same day. Infants with normal cUS at term age were found to have a normal MRI or only mild WM abnormalities on MRI at term age.