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Biomedical subjects

Vineta Fellman

Publications and source records attributed to Vineta Fellman.

At least 19 recordsLinked to original sources

No improvement in outcome of nationwide extremely low birth weight infant populations between 1996-1997 and 1999-2000.

OBJECTIVE: Our goal was to investigate whether outcome in extremely low birth weight infants changes over time in Finland. PATIENTS AND METHODS: All infants with a birth weight <1000 g born in Finland in 1996-1997 and 1999-2000 were included in the study. Perinatal and follow-up data were collected in a national extremely low birth weight infant research register. Data concerning cerebral palsy and visual impairment were obtained from hospitals, the national discharge, and visual impairment registers. RESULTS: A total of 529 and 511 extremely low birth weight infants were born during 1996-1997 and 1999-2000. No changes were detected in prenatal, perinatal, neonatal, and postneonatal mortality rates between the periods. The survival rates including stillborn infants were 40% and 44%. The incidence of respiratory distress syndrome and septicemia increased from 1996-1997 to 1999-2000 (75% vs 83% and 23% vs 31%). The overall incidence of intraventricular hemorrhage increased (29% vs 37%), but the incidence of intraventricular hemorrhage grades 3 through 4 did not (16% vs 17%). The rates of oxygen dependency at the age corresponding with 36 gestational weeks, retinopathy of prematurity stages 3 to 5, cerebral palsy, and severe visual impairment did not change. Mortality remained higher in 1 university hospital area during both periods compared with the other 4 areas, but no regional differences in morbidity were detected during the later period. CONCLUSIONS: No significant changes were detected in birth or mortality rate in extremely low birth weight infants born in Finland during the late 1990s, but some neonatal morbidities seemed to increase. Regional differences in mortality were detected in both cohorts. Repeated long-term follow-up studies on geographically defined very preterm infant cohorts are needed for establishing reliable outcome data of current perinatal care. Regional differences warrant thorough audits to assess causalities.

Cerebral Palsy↗

Neonatal frequency discrimination in 250-4000-Hz range: electrophysiological evidence.

OBJECTIVE: The precision of sound frequency discrimination in newborn infants in the 250-4000-Hz frequency range was determined using the neonatal electrophysiological mismatch response (MMR), the infant equivalent of adult mismatch negativity (MMN). METHODS: The electroencephalogram (EEG) was recorded in 11 full-term sleeping newborn infants mostly in active sleep (67% of the time). Pure tones were presented through loudspeakers in an oddball paradigm with a 800-ms stimulus onset asynchrony (SOA). Each stimulus block contained a standard (p=0.76) of 250, 1000, or 4000Hz in frequency (in separate blocks) and deviants with a frequency change of either 5% or 20% of the standard (p=0.12 of each). RESULTS: A positive ERP deflection was found at 200-300ms from stimulus onset in response to the 20% deviation from the 250, 1000, and 4000Hz standard frequencies. The amplitude of the response in the 200-300ms time window was significantly larger for the 20% than 5% deviation. CONCLUSIONS: We observed in newborn infants automatic frequency discrimination as reflected by a positive MMR. The newborns were able to discriminate frequency change of 20% in the 250-4000-Hz frequency range, whereas the discrimination of the 5% frequency change was not statistically confirmed. SIGNIFICANCE: The present data hence suggest that the neonatal frequency discrimination has lower resolution than that in adult and older children data.

Acoustic Stimulation↗

BCS1L is expressed in critical regions for neural development during ontogenesis in mice.

BCS1L is a chaperone necessary for the incorporation of Rieske FeS and Qcr10p into complex III (CIII) of the respiratory chain. Mutations in the BCS1L gene cause early fetal growth restriction and a lethal neonatal disease in humans, however, the pathogenesis remains unclear. Here, we analysed the expression of BCS1L during mouse embryonic development and compared its expression with that of the mitochondrial markers Porin, GRIM19, Core I, and Rieske FeS. BCS1L was strongly expressed in embryonic tissues already at embryonic days 7 (E7) and 9 whereas the expression of Porin and Rieske FeS was not as evident at this time point. At E11, BCS1L, Porin, and Rieske FeS had overlapping expression patterns in organs known to contain high numbers of mitochondria such as heart, liver and somites. In contrast, BCS1L was differently distributed compared to the mitochondrial proteins Porin, Rieske FeS, Core I and Grim 19 in the floor plate of the E11, E12 and E13 neural tube. These results show that the expression pattern of BCS1L only partially overlaps with the expression of Porin and Rieske FeS. Thus, BCS1L alone or in cooperation with Rieske FES may during development have previously unknown functions beside its role in assembly of complex III. The floor plate of the neural tube is essential for dorsal ventral patterning and the guidance of the developing neurons to their targets. The predominant expression of BCS1L in this region, together with its presence in peripheral ganglia from E13 onwards, indicates a role for BCS1L in the development of neural structures.

ATPases Associated with Diverse Cellular Activitie↗

Cortical auditory event-related potentials in newborn infants.

The possibility of recording changes in electroencephalography potentials following perception of sound was reported several decades ago. The recent expanding research on auditory cortical event-related potentials (AERPs) for assessing sound discrimination abilities in children and infants has indicated that several methodological issues need to be addressed before it can be implemented in clinical practice. Latencies, polarities, and amplitudes of the responses change with gestational age and during infancy. Thus, the maturation of the infant must be considered when designing stimulus paradigms and interpreting the responses. Of healthy newborn infants, only about 80% will show mismatch negativity, the automatic change detection of the auditory stimuli. Currently, the AERP method cannot be applied in clinical practice in the neonatal period, although the findings in healthy newborns at risk for dyslexia are promising. Further research will elucidate the possibility of developing AERPs as a possible early screening method during infancy for later dyslexia or cognitive dysfunction.

Dyslexia↗

Newborns discriminate novel from harmonic sounds: a study using magnetoencephalography.

OBJECTIVE: We investigated whether newborns respond differently to novel and deviant sounds during quiet sleep. METHODS: Twelve healthy neonates were presented with a three-stimulus oddball paradigm, consisting of frequent standard (76%), infrequent deviant (12%), and infrequent novel stimuli (12%). The standards and deviants were counterbalanced between the newborns and consisted of 500 and 750 Hz tones with two upper harmonics. The novel stimuli contained animal, human, and mechanical sounds. All stimuli had a duration of 300 ms and the stimulus onset asynchrony was 1s. Evoked magnetic responses during quiet sleep were recorded and averaged offline. RESULTS: Two deflections peaking at 345 and 615 ms after stimulus onset were observed in the evoked responses of most of the newborns. The first deflection was larger to novel and deviant stimuli than to the standard and, furthermore, larger to novel than to deviant stimuli. The second deflection was larger to novel and deviant stimuli than to standards, but did not differ between the novels and deviants. CONCLUSIONS: The two deflections found in the present study reflect different mechanisms of auditory change detection and discriminative processes. SIGNIFICANCE: The early brain indicators of novelty detection may be crucial in assessing the normal and abnormal cortical function in newborns. Further, studying evoked magnetic fields to complex auditory stimulation in healthy newborns is needed for studying the newborns at-risk for cognitive or language problems.

Acoustic Stimulation↗

Bilateral hemodynamic responses to auditory stimulation in newborn infants.

We studied hemodynamic auditory evoked responses of 20 healthy full-term neonates with near-infrared spectroscopy. The instrument used allows the measurements to be performed simultaneously above both auditory cortices. The stimulation consisted of 5-s trains of sound (700-ms interstimulus interval) with a 25-s silent interval. In response to the stimulation, a significant increase in concentration of oxygenated hemoglobin was detected in 14 out of 21 measurements. The mean latency of the largest response was 9.63+/-2.20 s (mean+/-SD) and the mean amplitude was 1.02+/-0.53 microM. The response amplitude was significantly larger in active (1.28+/-0.59 microM) than in quiet sleep (0.76+/-0.32 microM). The latency of the oxygenated hemoglobin concentration response was significantly shorter (r=-0.70 and p=0.0023) for infants with higher gestational age.

Acoustic Stimulation↗

A kind of auditory 'primitive intelligence' already present at birth.

'Primitive intelligence' in audition refers to the capacity of the auditory system to adaptatively model the acoustic regularity and react neurophysiologically to violations of such regularity, thus supporting the ability to predict future auditory events. In the present study, event-related brain potentials to pairs of tones were recorded in 11 human newborns to determine the infants' ability to extract an abstract acoustic rule, the direction of a frequency change. Most of the pairs (standard, P = 0.875) were of ascending frequency (i.e. the second tone higher than the first), while the remaining pairs (deviant, P = 0.125) were of descending frequency (the second tone being lower). Their frequencies varied among seven levels to prevent discrimination between standard and deviant pairs on the basis of absolute frequencies. We found that event-related brain potentials to deviant pairs differed in amplitude from those to standard pairs at 50-450 ms from the onset of the second tone of a pair, indicating the infants' ability to represent the abstract rule. This finding suggests the early ontogenetic origin of 'primitive intelligence' in audition that eventually may form a prerequisite for later language acquisition.

Acoustic Stimulation↗

Prothrombin and intraventricular haemorrhage.

UNLABELLED: In the study by Salonvaara et al., low prothrombin activity in preterm infants was associated with intraventricular haemorrhage (IVH). The interesting research question-do preterm infants who develop IVH have underlying coagulation disturbance?-could not be answered in this study. CONCLUSION: The association needs further investigation. The role of prothrombin in perinatal brain damage in the development of IVH and of white matter damage has to be further elucidated.

Cerebral Hemorrhage↗

Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997.

OBJECTIVE: Increasing survival of extremely low birth weight (ELBW; birth weight < 1000 g) infants raises a concern regarding the risks of adverse long-term outcome such as cognitive dysfunction. Few studies have reported long-term follow-up of representative regional cohorts. The objective of this study was to assess the 5-year outcome of a prospectively followed national ELBW infant cohort. METHODS: Of all live-born ELBW infants (n = 351) who were delivered in the 2-year period 1996-1997 in Finland, 206 (59%) survived until the age of 5 years. Of these, 103 were born at < 27 gestational weeks (GW). A total of 172 children were assessed with neurocognitive tests (Wechsler Preschool and Primary Scale of Intelligence-Revised and a Developmental Neuropsychological Assessment [NEPSY]). Nine children with cognitive impairment and inability to cooperate in testing were not assessed. Motor development was assessed with a modified Touwen test. RESULTS: The rate of cognitive impairment in the ELBW survivors was 9%. The rate of cerebral palsy was 14% (19% of ELBW infants who were born at < 27 GW). The mean full-scale IQ of the assessed children was 96 +/- 19 and in children of GW < 27 was 94 +/- 19. Attention, language, sensorimotor, visuospatial, and verbal memory values of NEPSY assessment were significantly poorer compared with normal population means. Four percent needed a hearing aid, and 30% had ophthalmic findings. Of 21 children who had been treated with laser/cryo for retinopathy of prematurity, 17 (81%) had abnormal ophthalmic findings. Of the whole cohort, 41 (20%) exhibited major disabilities, 38 (19%) exhibited minor disabilities, and 124 (61%) showed development with no functional abnormalities but subtle departures from the norm. Only 53 (26%) of the total ELBW infant cohort were classified to have normal outcome excluding any abnormal ophthalmic, auditory, neurologic, or developmental findings. Being small for gestational age at birth was associated with suboptimal growth at least until age 5. CONCLUSIONS: Only one fourth of the ELBW infants were classified as normally developed at age 5. The high rate of cognitive dysfunction suggests an increased risk for learning difficulties that needs to be evaluated at a later age. Extended follow-up should be the rule in outcome studies of ELBW infant cohorts to elucidate the impact of immaturity on school achievement and social behavior later in life.

Child Development↗

Speech-sound discrimination in neonates as measured with MEG.

Magnetic brain responses to speech sounds were measured in 10 healthy neonates. The stimulation consisted of a frequent vowel sound [a:] with a steady pitch contour, which was occasionally replaced by the vowel [i:] with a steady pitch, or the vowel [a:] with a rising pitch, manifesting a change of intonation. The magnetic mismatch-negativity response (MMNm) was obtained and successfully modelled to the speech sound quality change in all infants and to the intonation change in 6 infants. The present results indicate that auditory-cortex speech-sound discrimination may well be studied with magnetic recordings as early as in newborn infants.

Acoustic Stimulation↗

N-acetylcysteine administration during the first week of life does not improve lung function in extremely low birth weight infants.

Oxygen toxicity is thought to be an important factor involved in development of bronchopulmonary dysplasia (BPD) in the very preterm infant. Glutathione (GSH) plays a major role in the antioxidant defense system in the preterm lung and there are theoretical implications that N-acetylcysteine (NAC) treatment could improve its function. The purpose of this study was to investigate whether NAC treatment during the first week of life to preterm infants improved neonatal lung function as a measure of lung injury. The study was part of a multi-center Nordic controlled trial with prophylactic intravenous NAC treatment (16-32 mg/kg/day) for 6 days in newborn infants with birth weights 500-999 g. Lung mechanics, with calculations of compliance and resistance of the respiratory system, together with measurements of functional residual capacity and indices of gas mixing efficiency in the lung, were performed in 33 preterm infants (18 received NAC and 15 placebo) before discharge from the NICU. Median (range) gestational age was 25 (24-28) weeks in the NAC-treated infants and 25 (24-29) in the placebo group. Corresponding mean (SD) birth weights were 0.774 (0.11) and 0.761 (0.12) kg respectively. Lung function measurements did not show any significant differences between NAC-treated infants compared to placebo when examined before discharge from the NICU. We conclude that prophylactic NAC treatment to extremely low birth weight infants during the first week of life does not improve lung function at term.

Acetylcysteine↗

Atypical auditory event-related potentials in preterm infants during the first year of life: a possible sign of cognitive dysfunction?

We assessed auditory event-related potentials in small-for-gestational-age (SGA; 850 +/- 258 g, 28.9 +/- 3.3 gestational wk; n = 15) and appropriate for gestational age (AGA; 1014 +/- 231 g, 26.9 +/- 1.9 gestational wk; n = 20) preterm infants and healthy term infants (n = 22). An oddball paradigm was used with a harmonic tone of 500-Hz frequency as the standard and of 750-Hz frequency as the deviant stimulus. The preterm infants were studied at 40 gestational wk and at 6 and 12 mo of corrected age, and the control subjects were studied at 2-4 d and at 3, 6, 9, 12, and 15 mo of age. The peaks of interest were the main positive peak (P350), the negative peaks at 250 ms (N250) and 650 ms (Nc), and the mismatch negativity at 200 ms (MMN). At term, the P350 in the preterm infants was similar to that of the newborn control subjects. In response to the deviant, the Nc was smaller in the SGA than in the AGA (P < 0.02) and control (P < 0.005) infants. The N250 amplitude was also lower in the SGA infants. At 12 mo, the MMN was observed in the control but not in the preterm infants, whose broad difference positivity correlated with the Bayley developmental index. The decreased Nc and N250 peaks in the SGA infants may suggest an increased risk for cognitive dysfunction. The broad difference positivity at 1 y of age may indicate atypical cortical auditory processing. Whether cognitive dysfunction can be predicted by these findings needs to be assessed in a study with extended follow-up.

Cognition Disorders↗

Plasma 8-isoprostane is increased in preterm infants who develop bronchopulmonary dysplasia or periventricular leukomalacia.

Our aim was to assess the plasma free 8-epi-prostaglandin F(2alpha) (8-isoprostane) and ascorbyl radical as risk indicators for oxidative damage in extremely low birth weight infants (ELBWIs) and the effect of N-acetylcysteine (NAC) on these markers. Plasma samples were collected on days 3 and 7 of life from infants who were enrolled in a randomized, controlled trial in which i.v. NAC or placebo was administered to ELBWIs during the first week of life, with the aim of preventing bronchopulmonary dysplasia (BPD). Plasma 8-isoprostane was analyzed in 83 infants using an enzyme immunoassay kit. Ascorbyl radical concentration was measured in 61 infants with electron spin resonance spectroscopy. The 8-isoprostane concentrations were similar in the NAC and placebo groups. In infants who later developed BPD or died (n = 29), the median (range) 8-isoprostane concentration was significantly higher (p = 0.001) on day 3 and day 7 [50.0 pg/mL (19-360) and 57.0 pg/mL (14-460), respectively] than in survivors without BPD [n = 54; 34.5 pg/mL (5-240) and 39.5 pg/mL (7-400), respectively]. The 8-isoprostane levels increased significantly more (p < 0.05) in infants who later developed periventricular leukomalacia. NAC treatment or the later development of BPD was not related to the ascorbyl radical levels. The ascorbyl radical level decreased significantly in all groups from day 3 to day 7, but the difference between the groups was not significant. The mean (SD) ascorbyl radical level on day 3 was significantly higher (p < 0.01) in infants who later developed periventricular leukomalacia [287 (124) versus 194 (90)]. These data suggest that plasma 8-isoprostane could serve as a marker in assessing the risk for BPD development in ELBWIs.

Biomarkers↗

Haemodynamic effects of erythrocyte transfusion in preterm infants.

UNLABELLED: The aim of the study was to assess the short-term cardiorespiratory effects of a standard red cell transfusion in very low birth weight (< 1500 g) infants undergoing intensive care. A total of 37 infants (birth weight 920 +/- 230 g, gestational age 27.8 +/- 2.1 weeks, age at study 6.1 +/- 3.9 days) with indwelling arterial lines were studied when 10 ml/kg of packed donor red cells were transfused based on clinical judgment. Infants with patent ductus arteriosus and/or inotropic treatment were excluded from the study. Oxygen saturation, left ventricular output, stroke volume, systolic, diastolic and mean arterial pressure, heart rate, and capillary refill time were assessed immediately prior to the transfusion and within an hour after the transfusion was completed. Capillary refill time after the transfusion was significantly shorter than prior to the transfusion (2.1 +/- 0.9 versus 2.4 +/- 1.0 s, P = 0.033). Left ventricular output, stroke volume and arterial pressures remained unaltered. Oxygen saturation after the transfusion was lower than before the transfusion (94.0 +/- 3.8 versus 95.3 +/- 2.5%, P = 0.014) despite unaltered oxygen supply. CONCLUSION: the data suggest that although a red cell transfusion of 10 ml/kg may marginally improve peripheral perfusion, it does not influence cardiac output and arterial blood pressure in normotensive preterm infants. It may, however, cause a transient decrease in oxygen saturation.

Blood Pressure↗

Newborn human brain identifies repeated auditory feature conjunctions of low sequential probability.

Natural environments are usually composed of multiple sources for sounds. The sounds might physically differ from one another only as feature conjunctions, and several of them might occur repeatedly in the short term. Nevertheless, the detection of rare sounds requires the identification of the repeated ones. Adults have some limited ability to effortlessly identify repeated sounds in such acoustically complex environments, but the developmental onset of this finite ability is unknown. Sleeping newborn infants were presented with a repeated tone carrying six frequent (P = 0.15 each) and six rare (P approximately 0.017 each) conjunctions of its frequency, intensity and duration. Event-related potentials recorded from the infants' scalp were found to shift in amplitude towards positive polarity selectively in response to rare conjunctions. This finding suggests that humans are relatively hard-wired to preattentively identify repeated auditory feature conjunctions even when such conjunctions occur rarely among other similar ones.

Acoustic Stimulation↗

The newborn human brain binds sound features together.

To process a stimulus as a holistic entity, the human brain must be able to conjoin its different features. Previous evidence suggests that this ability emerges during the first months of life, implying its considerable dependence on postnatal development. We recorded human newborn (1-3 days of age) electrical brain responses to frequently occurring (standard) sounds and to rarely occurring (deviant) sounds in a series. Responses to deviants differed from those to standards despite the fact that only the combination of sound frequency and intensity could be used as a cue for discriminating between these sound types. Our finding suggests that the human brain is ready for auditory feature binding very soon after birth.

Acoustic Stimulation↗

Auditory magnetic responses of healthy newborns.

We recorded magnetic brain activity from healthy human newborns when they heard frequency changes in an otherwise repetitive sound stream. We were able to record the magnetic counterpart of the mismatch negativity (MMN) previously described only with electric recordings in infants. The results show that these recordings are possible, although still challenging due to the small head size and head movements. The modelling of the neural sources underlying the recorded responses suggests cortical sources in the temporal lobes.

Acoustic Stimulation↗