Biomedical subjects

Vineta Fellman

Publications and source records attributed to Vineta Fellman.

36 records · Page 2Linked to original sources

PubMed2003

Newborn infants can organize the auditory world.

The perceptual world of neonates is usually regarded as not yet being fully organized in terms of objects in the same way as it is for adults. Using a recently developed method based on electric brain responses, we found that, similarly to adults, newborn infants segregate concurrent streams of sound, allowing them to organize the auditory input according to the existing sound source. The segregation of concurrent sound streams is a crucial step in the path leading to the identification of objects in the environment. Its presence in newborn infants shows that the basic abilities required for the development of conceptual objects are available already at the time of birth.

Adult↗

PubMed2003

Cardiac hypertrophy and altered hemodynamic adaptation in growth-restricted preterm infants.

The objective was to elucidate hemodynamic adaptation in very low birth weight (<1500 g) infants after intrauterine growth retardation. 31 growth-retarded (SGA, birth weight <-2 SD) and 32 appropriate for gestational age (AGA, birth weight within +/- 1 SD range) infants were enrolled. In SGA infants, the diastolic diameters of the interventricular septum and the left ventricle were increased, and serum brain natriuretic peptide (BNP) was elevated. Left ventricular output (LVO) of the AGA infants increased from 150 +/- 28 to 283 +/- 82 mL/kg/min during the study (p < 0.01). The SGA infants had a higher initial LVO than the AGA infants (243 +/- 47 versus 150 +/- 28 mL/kg/min, p < 0.05), but did not show further LVO increase during the study period. Red cell (RCV) and blood (BV) volume were assessed by Hb subtype analysis, when packed donor red cells were transfused. RCV and BV did not differ between the groups initially, but RCV increased by 18% and BV by 29% in the AGA group during the first 3 d. On day 3, AGA infants had larger BV than the SGA infants (88 +/- 5 versus 73 +/- 12 mL/kg, p < 0.05). In conclusion, cardiac hypertrophy, elevated initial LVO and BNP of the SGA infants suggest increased cardiac workload after intrauterine growth retardation. Based on the BV and RCV data, blood volume regulation may also be impaired. The data suggest that SGA preterm infants may be exposed to an increased risk of circulatory failure during early adaptation.

Cardiomegaly↗

PubMed2003

Visual impairment in children born prematurely from 1972 through 1989.

PURPOSE: To investigate the incidence and causes of visual impairment in children born prematurely in Finland from 1972 through 1989, and to determine what conditions and factors were associated with its occurrence. DESIGN: Retrospective, cross-sectional study. SUBJECTS: All visually impaired individuals from 0 to 17 years of age who had been born at fewer than 37 gestational weeks in Finland from 1972 through 1989 for whom records were available in the Finnish Register of Visual Impairment were eligible for this study. METHODS: Data in the Finnish Register of Visual Impairment relating to 556 children were supplemented with data from hospital records, and from the Register of Births, the Register of Congenital Malformations, the Finnish Care Register, and the Finnish Cancer Register. Data relating to causes associated with visual impairment in particular were collected. Data relating to the children born prematurely were compared with data relating to children born at full term. The chi-square test (Mantel-Haenszel), the Mann-Whitney U test, Fisher exact test, and stepwise logistic regression analysis were used in statistical analysis of the data. MAIN OUTCOME MEASURES: Visual acuity, ophthalmologic diagnoses, associated systemic disease, multiple handicap, gestational age, birth weight, 5-minute Apgar scores, and prenatal, perinatal, and infantile or juvenile disorders or disease and treatment. RESULTS: One hundred twenty-five of the 556 visually impaired children (23%; 11/100000 children less than 18 years of age) had been born preterm. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment (in 46%, 28%, and 12% of cases, respectively). Sixty-six percent of those born prematurely with visual impairment were also affected by other handicaps (mental, motor, auditory), 54% by cerebral palsy and 36% by epilepsy. Eighty-eight of the 125 children (70%) born preterm with visual impairment were blind. Very low birth weight (<1500 g), young gestational age (fewer than 30 weeks), prenatal infection, hyperbilirubinemia, respiratory disorders, asphyxia, and lengthy mechanical ventilation were associated with an increased risk of visual impairment. CONCLUSIONS: Premature birth was a major risk factor of severe visual impairment and blindness in childhood. The visual impairment often was accompanied by cerebral palsy, epilepsy, and other motor and mental handicaps. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment. During the 18 years covered by the study, the increasing incidence of survival of infants born weighing fewer than 1500 g was associated with increasing incidence of blindness.

Adolescent↗

PubMed2003

N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants: a randomized controlled trial.

OBJECTIVE: To evaluate whether N-acetylcysteine (NAC) infusion during the first week of life reduces the risk of death or bronchopulmonary dysplasia (BPD) in infants with extremely low birth weight. Study design In a Nordic multicenter, double-blind trial, infants (n=391) weighing 500 to 999 g and on ventilator or nasal continuous positive airway pressure were randomized before the age of 36 hours to receive NAC 16 to 32 mg/kg/d (n=194) or placebo (n=197) intravenously for 6 days. Primary end points were death or BPD, defined as supplementary oxygen requirement at 36 weeks' gestational age. RESULTS: There was no difference in the combined incidence of the primary end points death or BPD, 51% vs. 49%, between the NAC group and control group. Also similar was the incidence of BPD in survivors at 36 weeks' gestational age, 40% vs. 40%, and the mean oxygen requirement at the age of 28 days, 31.2% vs. 30.7%, respectively. The severity of BPD was similar in both groups. CONCLUSIONS: A 6-day course of intravenous N-acetylcysteine at the dosage used does not prevent BPD or death in infants with extremely low birth weight.

Antioxidants↗

PubMed2003

Economic costs of care in extremely low birthweight infants during the first 2 years of life.

OBJECTIVE: To assess the 2-yr costs of extremely low birthweight infants' (ELBWIs; birthweight, < 1000 g) care in relation to birthweight, outcome, and the costs of normal birthweight infants. DESIGN: Cost data were obtained from care-giving hospitals and by a parental questionnaire. Outcome data from the perinatal and neonatal periods and from the first 2 yrs for both ELBWIs and control infants had been prospectively collected to a national ELBWI register. PATIENTS: We studied 71 ELBWIs and 60 normal birthweight controls born in Helsinki University Hospital in 1996-1997. MEASUREMENTS: Collected data comprised costs resulting from care of ELBWIs and normal birthweight control infants and included hospital, outpatient care, medication, rehabilitation, auxiliary means, and travel costs; ancillary costs from daily care; parent's accommodation during hospitalization periods; and loss of earnings during the infant's first 2 yrs. MAIN RESULTS: The average total 2-yr healthcare cost was 104,635 Euros for surviving ELBWIs and 3,135 Euros for control infants. In ELBWIs, initial hospital costs alone accounted for 64% of total costs; the costs during the first and second postdischarge years accounted for 20% and 13%, respectively. The mean hospital cost of nonsurviving ELBWIs was 19,950 Euros. A normally developed ELBWI had costs 25-fold, a mildly disabled ELBWI had costs 33-fold, and a severely disabled ELBWI had costs 68-fold those of control infants. Birthweight correlated negatively with intensive care costs but did not correlate with costs after initial discharge. CONCLUSION: Total costs of ELBWIs decreased over time up to the age of 2 yrs, but even in normally developed ELBWIs, costs remained higher than those of normal birthweight infants. Low birthweight seemed to be related to increased initial hospital costs but not to annual costs after the first discharge.

Birth Weight↗

PubMed2003

Blood volume assessment with hemoglobin subtype analysis in preterm infants.

The aim of the study was to assess plasma volume (PV) and red cell volume (RCV) in preterm infants with a liquid chromatographic hemoglobin subtype method (HbST) based on dilution of autologous fetal hemoglobin (HbF) by donor adult hemoglobin and measurement of the amount of HbF. PV determination with the indocyanine green dye dilution technique (ICG) was used as a reference method. Eight infants, median gestational age 29.8 weeks (range 27.6-30.9 weeks) and median birth weight 1,300 g (range 1,030-1,760 g), were studied at a median age of 3.0 days (range 1-6 days). RCV was 33.6 +/- 12 ml/kg measured with ICG and 32.1 +/- 5.2 ml/kg with HbST. PV was 47.0 +/- 18 and 40.2 +/- 6.6 ml/kg, respectively. There was a close correlation between the RCVs measured with the two techniques (Pearson correlation 0.83, p < 0.05). In conclusion, HbST provides a reliable and safe determination of RCV in preterm infants.

Birth Weight↗

PubMed2002

Maturation of the auditory change detection response in infants: a longitudinal ERP study.

Mismatch negativity (MMN) is a negative component of auditory event-related potential (ERP), reflecting the brain's automatic change detection process. In the present study we investigated the development of the pitch change detection, as indexed by the MMN, in the same infants from birth until 12 months of age. The MMN was identified in approximately 75% of infants at each age, being relatively stable in latency and amplitude at the group level across the ages studied. However, within the same subjects the MMN substantially varied from age to age. The inspection of individual data revealed a possible source of this variability: in a portion of 3- to 9-month-old infants, a large-amplitude positive component commenced at the latency of the MMN and thus might have masked it. The results of the additional experiment, employing distracting novel sounds in 2-year-old infants and newborns, suggested that the observed positive component could represent an infant analogue of the adult P3a response, indexing an involuntary orienting of attention. Therefore, the variability from age to age might be, at least partially, caused by the differences in degree of infants' orienting, resulting in the reduction of the scalp recorded mismatch negativity in recordings when the orienting P3a positivity was elicited.

Acoustic Stimulation↗

PubMed2002

A newborn with domestically acquired legionnaires disease confirmed by molecular typing.

Legionella pneumophila serogroup 6 was recovered from a bronchoalveolar lavage specimen from a 1-week-old, full-term newborn with pneumonia, as well as from water samples from the maternity hospital and the newborn's home (an apartment). Amplified fragment-length polymorphism typing revealed that the strains isolated from the newborn and her home were indistinguishable from each other but were clearly different from the hospital and control strains. To our knowledge, this is the first report of domestic acquisition of legionnaires disease in a newborn to have been confirmed by molecular typing.

DNA, Bacterial↗

PubMed2002

GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L.

GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death) syndrome is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. We previously localized the causative gene to a 1.5-cM region on chromosome 2q33-37. In the present study, we report the molecular defect causing this metabolic disorder, by identifying a homozygous missense mutation that results in an S78G amino acid change in the BCS1L gene in Finnish patients with GRACILE syndrome, as well as five different mutations in three British infants. BCS1L, a mitochondrial inner-membrane protein, is a chaperone necessary for the assembly of mitochondrial respiratory chain complex III. Pulse-chase experiments performed in COS-1 cells indicated that the S78G amino acid change results in instability of the polypeptide, and yeast complementation studies revealed a functional defect in the mutated BCS1L protein. Four different mutations in the BCS1L gene have been reported elsewhere, in Turkish patients with a distinctly different phenotype. Interestingly, the British and Turkish patients had complex III deficiency, whereas in the Finnish patients with GRACILE syndrome complex III activity was within the normal range, implying that BCS1L has another cellular function that is uncharacterized but essential and is putatively involved in iron metabolism.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2002

ABCB6 (MTABC3) excluded as the causative gene for the growth retardation syndrome with aminoaciduria, cholestasis, iron overload, and lactacidosis.

GRACILE syndrome (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death; OMIM 603358) is a rare metabolic disorder with autosomal recessive mode of inheritance. So far it has been diagnosed only in patients with Finnish ancestors. The GRACILE locus has been positioned to a restricted region of chromosome 2q33-37, but the causative gene remains to be identified. The ABCB6 gene, involved in iron homeostasis, mitochondrial respiratory function, and maintenance of the stability of mitochondrial DNA, has been positioned to this same chromosomal region, and advocated in literature as a highly probable candidate gene for the syndrome on both functional and positional grounds. We carried out sequence and quantitative expression analyses to detect potential disease-associated mutations in the ABCB6 gene. No mutations in the coding region of ABCB6 were found, and the expression level of ABCB6 in patient fibroblasts was found to be comparable to controls. Haplotype analysis of the critical DNA region provided evidence for positional exclusion also. Based on these data, ABCB6 is not the causative gene for GRACILE syndrome.

ATP-Binding Cassette Transporters↗

PubMed2002

Maturation of the auditory event-related potentials during the first year of life.

This study examined the maturation of cortical auditory event-related potentials (ERPs) from birth until 12 months of age. In the 15 infants studied, all ERP peaks observable at 12 months of age, the P150, N250, P350, and N450 were identifiable already at birth, As in previous studies, the amplitudes of the ERP peaks increased and latencies shortened with increasing age. In addition, the time courses of the amplitude growth of these peaks differed from each other. It was concluded, that the generators of all the infantile ERP peaks are functional already at birth, and that the maturational changes in the waveform morphology can mostly be accounted for by the changing relative strengths of the different generators.

Acoustic Stimulation↗

PubMed2002

Event-related potential features indexing central auditory discrimination by newborns.

Behavioral research has produced little evidence on sound feature discrimination in neonates. Sensory processes underlying sound perception can be studied using the mismatch negativity (MMN) component of auditory event-related potentials (ERPs), which is not contingent on conscious perception and response. Thus, MMN is suitable for studying newborns, who are difficult to obtain behavioral responses from. The present study thus utilized spectrally rich sounds, known to elicit the most replicable MMN in adults, to investigate newborns' preattentive analysis of sound duration and frequency changes. An attempt was also made to control for the obligatory ERP effects on the MMN. Three-partial harmonic tones were presented in Duration and in Frequency oddball conditions to 55 newborns. In the other two, Equiprobable duration and Equiprobable frequency, conditions frequency and duration deviants of the oddball paradigms were presented with equal probabilities among sounds of other durations and frequencies. MMN was elicited in 81% of newborns in Frequency oddball condition and in 78% of newborns in Duration oddball condition. No significant amplitude differences between the duration and frequency MMNs were found, but MMN latency was delayed in Duration condition. The obligatory components seemed to contribute significantly to the deviant-standard difference in Duration but not in Frequency condition. The majority of neonates appear to possess effective sound frequency and duration discrimination mechanisms. Their preattentive sound discrimination is facilitated by spectrally rich sound content. The present findings support a change-detection nature of MMN in neonates; however, sound duration-related obligatory effects need to be taken into account in infant MMN studies.

Acoustic Stimulation↗

PubMed2002

Antenatal diagnosis of hereditary fetal growth retardation with aminoaciduria, cholestasis, iron overload, and lactic acidosis in the newborn infant.

OBJECTIVE: A prenatal diagnosis of the fetus for a mother of two previously deceased infants who died from the recently described autosomal recessive disease (OMIM 603358). The infants presented with intrauterine growth retardation, aminoaciduria, cholestasis, iron overload, severe lactic acidosis, and early death (GRACILE syndrome). STUDY DESIGN: DNA was extracted from the fibroblasts and tissue samples of the deceased infants, parental leukocytes, and from a chorion villus biopsy in the next pregnancy. Haplotypes were determined using the relevant markers flanking the disease-associated region of chromosome 2. RESULTS: Both deceased infants were homozygous for the four critical markers. The fetal haploptypes were identical to those of the siblings and the pregnancy was terminated. The iron content of the fetal liver was increased (5000 microg/g) compared with the controls, with a marked iron accumulation in the Kupffer cells. CONCLUSIONS: Antenatal diagnosis can be performed based on linkage analysis in families with at least one affected child because the disease locus has been assigned to a restricted chromosomal region. Typical histological abnormalities may be present in early fetal life.

Abortion, Induced↗

PubMed2002

Intrauterine growth restriction and postnatal steroid treatment effects on insulin sensitivity in preterm neonates.

OBJECTIVES: To study whether intrauterine growth restriction (IUGR) is associated with decreased sensitivity to the main fetal growth factor, insulin, and the effect of glucocorticoid therapy on insulin sensitivity in preterm infants. STUDY DESIGN: Newborn infants with a birth weight (BW) of< 1500 g were classified as appropriate for gestational age ([AGA], BW within +/- 1 SD, n = 10), or small for gestational age ([SGA], BW <-2 SD, n = 13); 5 AGA infants and 8 SGA infants received systemic steroids. An abbreviated modified minimal model test was performed, consisting of sequential blood samples for glucose and insulin assays, and intravenous infusions of 0.3 g/kg glucose and 0.02 U/kg regular human insulin. The insulin sensitivity index (S(I)) was calculated using a computer program. RESULTS: The basal insulin/glucose ratio (I/G) and S(I) did not differ between the AGA and SGA groups. Steroids did not influence the I/G nor the S(I) of AGA infants (10.2 +/- 6.7 vs 8.2 +/- 2.3), but decreased the S(I) in the SGA group (12.2 +/- 5.1 vs 5.3 +/- 2.7, P <.05). CONCLUSIONS: Insulin sensitivity of neonates can be measured by the modified minimal model. IUGR is not associated with impaired fetal glucose tolerance. Early neonatal steroid treatment decreases insulin sensitivity in SGA infants, which may contribute to their risk of having hyperglycemia.

Blood Glucose↗

PubMed2002

The auditory sensory memory trace decays rapidly in newborns.

The present study investigated the temporal dynamics of auditory sensory memory in newborns as reflected by the mismatch negativity (MMN), a preattentive electric change-detection response. MMN was obtained from 24 full-term healthy newborns who were either awake or asleep (quiet or active sleep) during the experiments. Stimuli were 1,000 Hz tones (standards) that were occasionally replaced by 1,100 Hz tones (deviants). The constant stimulus onset asynchrony (SOA) was, in separate blocks, either 450, 800, or 1,500 ms. A prominent MMN was obtained at the 800 ms SOA in all three sleep or waking states, whereas no MMN occurred at 450 and 1,500 ms SOAs. In view of the fact that in adults MMN is elicited even with a 10s SOA, these results imply that the time span of auditory memory is considerably shorter in neonates than in adults and 8-12-year-old children.

Auditory Perception↗

PubMed2002

Electric brain responses obtained from newborn infants to changes in duration in complex harmonic tones.

Event-related brain potentials of 10 full-term newborns in response to duration changes in complex, harmonic tones known to elicit prominent mismatch negativity (MMN) response in adults were investigated. Here we report that duration changes elicited prominent MMN responses in a 11 newborns tested. In contrast, MMN has been reported in as little as 50% of the infants in some previous studies using other sound attributes. When the infant MMN latency was compared with that obtained from adults, and 4- as well as 8-year-old children, it was found that the MMN latency was a bit later in newborns than in older age groups. This result is consistent with previous findings. The MMN amplitude, however, was surprisingly large in infants compared to older children.

Acoustic Stimulation↗

PubMedDate not supplied

The GRACILE syndrome, a neonatal lethal metabolic disorder with iron overload.

GRACILE syndrome (Fellman syndrome, MIM 603358), an autosomal recessive metabolic disorder of the Finnish disease heritage, has been diagnosed in 25 infants of 18 families. The incidence is at least 1/47,000 in Finland. The main findings are fetal growth retardation, Fanconi type aminoaciduria, cholestasis, iron overload (liver hemosiderosis, hyperferritinemia, hypotransferrinemia, increased transferrin iron saturation, and free plasma iron), profound lactic acidosis, and early death. The pathophysiology of the metabolic disturbance is unsolved. No significant deficiency of complex III activity of respiratory chain has been found, although we recently showed that the underlying genetic cause is a missense mutation (S78G) in the BCS1L gene and other mutations in that gene have been associated with complex III deficiency. BCS1L encodes a mitochondrial protein, acting as a chaperone in the assembly of complex III. Iron accumulation in liver, a typical feature being less abundant with increasing age, might be a primary abnormality or a secondary phenomenon due to liver dysfunction. In order to decrease the iron overload, three infants have been repeatedly treated with apotransferrin followed by exchange transfusion. Improvement in iron biochemistry occurred, but no clear beneficial effect on the clinical condition was found. Further studies will elucidate the role of iron in the pathophysiology of the disease.

ATPases Associated with Diverse Cellular Activitie↗

PubMedDate not supplied

Pathology of lethal fetal growth retardation syndrome with aminoaciduria, iron overload, and lactic acidosis (GRACILE).

Autopsy study of 17 newborn infants with lethal autosomal recessive disease presenting as growth retardation with lactic acidosis, Fanconi aminoaciduria, and hepatic hemosiderosis is reported. The patients succumbed between day 1 and 4 months of life; 9 patients died within the first month. All patients showed severe pathologic changes of liver with cholestasis in all livers. Extensive accumulation of stainable iron of the hepatocytes was present in 9/17 autopsy tissues and in two biopsy specimens. Moderate to abundant iron storage in the Kupffer cells was seen in all liver specimens. The amount of hepatocytic iron was high in livers up to 1 month of age and decreased thereafter. The general features and liver findings of this disorder suggest the name Growth Retardation Aminoaciduria Cholestasis Iron Overload, Lactacidosis and Early Death (GRACILE, OMIM 603358). Calcified concrements were seen in the medulla of 13/16 kidney specimens. Pancreas of 13/14 patients showed interstitial fibrosis and exocrine atrophy. Various pathologic findings such as renal tubular dysgenesis, paucity of hepatic bile ducts and iron storage in the macrophages of spleen and pulmonary alveoli were observed in some cases. Previous extensive clinical genetic and laboratory investigations have revealed that the patients had a previously unrecognized genetic disease. It is inherited as an autosomal recessive trait. The gene locus is 2q33-37. The basic defect of the disease remains unknown.

Acidosis, Lactic↗