Guy Kongolo

Syllabic discrimination in premature human infants prior to complete formation of cortical layers

The ontogeny of linguistic functions in the human brain remains elusive. Although some auditory capacities are described before term, whether and how such immature cortical circuits might process speech are unknown. Here we used functional optical imaging to evaluate the cerebral responses to syllables at the earliest age at which cortical responses to external stimuli can be recorded in humans (28- to 32-wk gestational age). At this age, the cortical organization in layers is not completed. Many neurons are still located in the subplate and in the process of migrating to their final location. Nevertheless, we observed several points of similarity with the adult linguistic network. First, whereas syllables elicited larger right than left responses, the posterior temporal region escaped this general pattern, showing faster and more sustained responses over the left than over the right hemisphere. Second, discrimination responses to a change of phoneme (ba vs. ga) and a change of human voice (male vs. female) were already present and involved inferior frontal areas, even in the youngest infants (29-wk gestational age). Third, whereas both types of changes elicited responses in the right frontal region, the left frontal region only reacted to a change of phoneme. These results demonstrate a sophisticated organization of perisylvian areas at the very onset of cortical circuitry, 3 mo before term. They emphasize the influence of innate factors on regions involved in linguistic processing and social communication in humans.

Coupled oxygenation oscillation measured by NIRS and intermittent cerebral activation on EEG in premature infants.

Electroencephalography of premature neonates shows a physiological discontinuity of electrical activity during quiet sleep. Near infrared spectroscopy (NIRS) shows spontaneous oscillations of hemoglobin oxygenation and volume. Similar oscillations are visible in term neonates and adults, with NIRS and other functional imaging techniques (fMRI, Doppler, etc.), but are generally thought to result from vasomotion and to be a physiological artifact of limited interest. The origin and possible relationship to neuronal activity of the baseline changes in the NIRS signal have not been established. We carried out simultaneous EEG-NIRS recordings on six healthy premature neonates and four premature neonates presenting neurological distress, to determine whether changes in the concentration of cerebral oxy- and deoxy- and total hemoglobin were related to the occurrence of spontaneous bursts of cerebral electric activity. Bursts of electroencephalographic activity in neonates during quiet sleep were found to be coupled to a transient stereotyped hemodynamic response involving a decrease in oxy-hemoglobin concentration, sometimes beginning a few seconds before the onset of electroencephalographic activity, followed by an increase, and then a return to baseline. This pattern could be either part of the baseline oscillations or superimposed changes to this baseline, influencing its shape and phase. The temporal patterns of NIRS parameters present an unique configuration, and tend to be different between our healthy and pathological subjects. Studies of physiological activities and of the effects of intrinsic regulation on the NIRS signal should increase our understanding of these patterns and EEG-NIRS studies should facilitate the integration of NIRS into the set of clinical tools used in neurology.

Effect of Domperidone on QT Interval in Neonates

OBJECTIVES To determine whether oral domperidone is associated with QT interval prolongation and ventricular arrhythmia and to identify factors that can influence these effects. STUDY DESIGN An electrocardiogram was performed before and after oral administration of domperidone in 31 neonates or infants classified into 3 groups according to gestational age. RESULTS Oral domperidone is associated with QTc prolongation except in infants with a gestational age less than 32 weeks of amenorrhea (P < .005). Mean QTc prolongation was 14 msec. On univariate analysis, oral domperidone-induced QTc prolongation was correlated with gestational age, birth weight, and elevated serum potassium. On multivariate analysis, after adjustment for gestational age, serum potassium was the only factor independently associated with interval QT prolongation during treatment. No ventricular arrhythmias were observed. CONCLUSIONS This study shows a significant association between oral domperidone therapy and QTc prolongation. Two risk factors were identified: advanced gestational age and serum potassium at the upper limit of normal. It is recommended that measurement of the QT interval be done before and after oral domperidone therapy.

High-resolution electroencephalography and source localization in neonates.

Although Electroencephalography (EEG) source localization is being widely used in adults, this promising technique has not yet been applied to newborns because of technical difficulties, such as lack of data concerning the newborn skull conductivity, thickness, and homogeneity. Using a new type of EEG headcap molded on each babys head, we aimed to determine whether this technique could be adapted to neonates, and to evaluate the importance of these technical difficulties. We carried out EEG source reconstruction of the recordings of five neonates using dipole fit algorithm. We used four different head models for each neonate, obtained from individual MRI scans: normal skull thickness and conductivity of 0.0042 S/m; normal thickness and conductivity of 0.33 S/m; increased thickness and conductivity of 0.0042 S/m; and normal thickness and conductivity with a modeled bregma fontanel. Dipole locations were consistent with MRI and clinical data. The mean difference between the dipole locations in the 0.0042 and the 0.33 S/m skull layer models was 11.6 ± 2.5 mm, with an average 29.7% decrease in magnitude for the 0.33 S/m model but no significant changes for the dipoles orientation. Skull layer thickness had a large influence on magnitude, but no significant effect on position and orientation. The mean difference between the dipole locations induced by the modeled fontanel was 2.0 ± 2.1 mm, with an average 2.1% increase in magnitude. Our results show that EEG source localization is feasible in neonates. With further development, the technique may prove useful for neurological evaluation of neonates. Hum Brain Mapp, 2008.

(1–3)-β-D-glucan levels in candidiasis infections in the critically ill neonate

Introduction: The diagnosis of neonatal invasive Candida infections (ICIs) is problematic because the clinical signs are not specific and blood cultures are rarely positive. Hence, new diagnostic markers are needed. Objective: To assess the contribution of serum (1–3)-β-d-glucan (BDG) levels to the diagnosis of neonatal ICIs and to analyse the change in this parameter during antifungal therapy. Methods: This retrospective study (December 2010-March 2012) was performed at Amiens University Medical Center (Amiens, France). We included newborns in whom a BDG assay was performed for a suspected ICI and classified as infected (n = 18) or non-infected (n = 43). Results: Sixty-one patients (median (IQR) gestational age: 28.5 weeks (26.7–30.6); birth weight: 1000 g (910–1440)) were included. The BDG level was higher in the infected group (364 pg/ml (131–976) vs. 89 pg/ml (30–127); p < 0.001). The optimal BDG cut-off for distinguishing between non-infected and infected patients was 125 pg/ml (Se = 84%, Sp = 75%). The BDG level fell over the course of antifungal therapy. Conclusion: Our study results suggest that BDG levels were increased in neonatal invasive Candida infections (cut-off for BDG positivity > 125 pg/ml). The change in the serum BDG levels may be of value in evaluating the efficacy of antifungal therapy.

Relationship Between Functional Residual Capacity and Oxygen Desaturation During Short Central Apneic Events During Sleep in “Late Preterm” Infants

Apneic episodes are frequent in the preterm neonate and particularly in active sleep (AS), when functional residual capacity (FRC) can be decreased. Furthermore, FRC may be inversely correlated with the speed of blood-O2-desaturation. We evaluated the potential involvement of FRC in the mechanisms responsible for blood-O2-desaturation during short central apneic events (>3 s) in “late-preterm” infants and analyzed the specific influence of sleep state. Apneic events were scored in 29 neonates (postmenstrual age: 36.1 ± 1.2 wk) during AS and quiet sleep (QS). FRC was measured during well-established periods of regular breathing. Apneas with blood-O2-desaturation (drop in SpO2 >5% from the baseline, lowest SpO2 during apnea: 91.4 ± 1.8%) were more frequent in AS than in QS, whereas no difference was seen for apneas without desaturation. The magnitude of the FRC did not depend on the sleep state. In AS only, there was a negative relationship between FRC and the proportion of apneas with desaturation. Even in late preterm infants who do not experience long-lasting apnea, blood-O2-desaturation during short apneic events is related (in AS but not QS) to a low baseline FRC. Sleep stage differences argue for a major role of AS-related mechanisms in the occurrence of these apneas.

Inverse coupling between respiratory and cardiac oscillators in a life-threatening event in a neonate

The authors report the case of a baby boy born at a gestational age of 32 weeks who experienced a life-threatening event triggered by vagal overactivity, associated with a transient phase of inverse coupling with a 1:1 phase ratio between ECG and respiration, resulting in respiratory arrest. This case report highlights the vital importance of coupling between cardiac and respiratory oscillators, especially in premature infants or neonates.

Involvement of Autonomic Nervous Activity Changes in Gastroesophageal Reflux in Neonates during Sleep and Wakefulness

Background It has been suggested that disturbed activity of the autonomic nervous system is one of the factors involved in gastroesophageal reflux (GER) in adults. We sought to establish whether transient ANS dysfunction (as assessed by heart rate variability) is associated with the occurrence of GER events in neonates during sleep and wakefulness. Methods Nineteen neonates with suspected GER underwent simultaneous, synchronized 12-hour polysomnography and esophageal multichannel impedance-pH monitoring. We compared changes in HRV parameters during three types of periods (control and prior to and during reflux) with respect to the vigilance state. Results The vigilance state influenced the distribution of GER events (P<0.001), with 53.4% observed during wakefulness, 37.6% observed during active sleep and only 9% observed during quiet sleep. A significant increase in the sympathovagal ratio (+32%, P=0.013) was observed in the period immediately prior to reflux (due to a 15% reduction in parasympathetic activity (P=0.017)), relative to the control period. This phenomenon was observed during both wakefulness and active sleep. Conclusion Our results showed that GER events were preceded by a vigilance-state-independent decrease in parasympathetic tone. This suggests that a pre-reflux change in ANS activity is one of the factors contributing to the mechanism of reflux in neonates.

Realistic Head Model Design and 3D Brain Imaging of NIRS Signals Using Audio Stimuli on Preterm Neonates for Intra-Ventricular Hemorrhage Diagnosis

In this paper we propose an auditory stimulation and near infra-red spectroscopy (NIRS) hemodynamic changes acquisition protocol for preterm neonates. This study is designed to assess the specific characteristics of neurovascular coupling to auditory stimuli in healthy and ill neonate brains. The method could lead to clinical application in intra-ventricular hemorrhage (IVH) diagnosis along with other techniques such as EEG. We propose a realistic head model creation with all useful head structures and brain tissues including the neonate fontanel for more accurate results from NIRS signals modeling. We also design a 3D imaging tool for dynamic mapping and analysis of brain activation onto the cortex surface. Results show significant differences in oxy-hemoglobin between healthy neonates and subjects with IVH.

Blood product transfusions are associated with an increase in serum (1-3)-beta-d-glucan in infants during the initial hospitalization in neonatal intensive care unit (NICU)

Abstract Introduction: Serum (1-3)-beta-d-glucan (BDG) assay has been proposed as an adjunct for the rapid diagnosis of invasive fungal infection (IFI). However, false-positive results have been reported following transfusion of blood products in adults. Aims: To assess the relationship between blood product transfusion and elevated BDG in neonates. Method: Retrospective study including neonates ≤32 weeks, with no fungal colonization or infection, in whom BDG assay was performed for suspicion of IFI. Patients were classified in Transfusion (n = 78) and No Transfusion (n = 55) groups depending on whether or not they were transfused. Clinical, biochemical and microbiological characteristics were recorded. A BDG assay >80 pg/mL was considered as positive. Statistical analyses: bivariate and multivariate logistic regression. Results (median, IQR): One hundred and thirty-three infants were included (gestational age 28.4 weeks, 26.9–30; birth weight 1000 g, 847–1300). BDG was higher in the Transfusion group (170 pg/mL, 65–317) than in the No Transfusion group (57 pg/mL, 34–108; p < 0.001). False-positive BDG assay results were associated with red blood cells (RBC) and fresh frozen plasma (FFP) transfusions. Conclusion: BDG is increased after RBC and FFP transfusions in neonates, leading to overdiagnosis of IFI. Fungal colonization status in peripheral sites and central cultures could help to reduce the risk of misdiagnosis.