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.     

Auditory event-related potentials and cognitive function of preterm children at five years of age.

OBJECTIVE: In our previous study, auditory event-related potentials (AERPs) in preterm 1-year-old children had a positive deflection at 150-350 ms that correlated positively with their 2-year neurodevelopmental outcome. In a study of the same subjects at age 5, our aim was to assess AERPs and their relationship to neuropsychological test results. METHODS: Preterm small (SGA, n=13), appropriate for gestational age (AGA, n=15), and control (n=13) children were assessed with an Easy paradigm presenting a large frequency change accompanied with occasional novel sounds, and a Challenging paradigm presenting small frequency and duration changes with a rapid rate. The preterm children underwent neurocognitive tests. RESULTS: Easy paradigm. The P1 response to frequency deviant was smaller and MMN larger in the preterm than in the control children. Challenging paradigm. The P1 response to standard, frequency, and duration deviants was smaller in the preterm than in the control children. The N2 response to frequency deviant was larger in the preterm than in the control children. AGA and SGA children had similar AERPs. The P1, N2, and MMN amplitudes correlated with verbal IQ and NEPSY language subtests. CONCLUSIONS: Small P1 response(s) appears to be typical for preterm children. SIGNIFICANCE: Small P1 response in preterm children may suggest altered primary auditory processing.     

Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants

Background: Reactive oxygen species have been considered to play a role in several clinical complications in pre-term infants. The aim of this study was to determine the pharmacokinetics of intravenous N-acetylcysteine in pre-term neonates. This information is needed to evaluate the use of N-acetylcysteine as an antioxidant in this patient group. Methods: N-acetylcysteine was infused intravenously in ten patients (gestational age 24.9–31.0 weeks, weight 500–1384 g) for 24 h (3.4–4.6 mg/kg/h), starting 2.0–11.2 h from birth (study I) and in six patients (gestational age 25.9–29.7 weeks, weight 520–1335 g) for 6 days (0.3–1.3 mg/kg/h), starting at the age of 24 h (study II). Arterial plasma N-acetylcysteine and cyst(e)ine concentrations were determined from timed samples taken during (study I and II) and after (study I) the N-acetylcysteine infusion. Results: In study I, the mean elimination half-life of N-acetylcysteine was 11 h (range 7.8–15.2 h). The mean plasma clearance of N-acetylcysteine was 37 ml/kg/h (range 13–62 ml/kg/h) and the mean volume of distribution was 573 ml/kg (range 167–1010 ml/kg). The plasma clearance and volume of distribution correlated with weight (r = 0.81, P < 0.01, and r = 0.78, P < 0.01, respectively) and with gestational age (r = 0.71, P < 0.05, and r = 0.64, P < 0.05, respectively). In study II, the steady-state concentration of N-acetylcysteine was reached in 2–3 days in five of six patients during a constant infusion. Conclusions: The pharmacokinetics of N-acetylcysteine in pre-term infants depend markedly on weight and gestational age. The elimination of N-acetylcysteine is much slower in pre-term new-borns than in adults. Received: 12 April 1999 / Accepted in revised form: 18 August 1999     

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.     

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 2q 33-37. The basic defect of the disease remains unknown.     

Alfentanil as procedural pain relief in newborn infants.

AIMS: To assess the need for, and the suitability of, alfentanil for pain relief during tracheal suction used in assisted ventilation in newborn infants. METHODS: In a randomised, controlled, double blind, crossover trial, placebo (10 micrograms/kg) and 20 micrograms/kg alfentanil were infused in random order two minutes before three separate endotracheal suctions, at least six hours apart, to 10 infants. Measurements were made of physiological variables, behaviour, and stress hormones. RESULTS: After placebo infusion heart rate significantly increased (median 14; interquartile range 12-16 beats/minute) as did behavioural pain score (5; 3-5). Alfentanil (20 micrograms/kg) attenuated the heart rate increase, normalised the pain score, and caused a decrease in plasma adrenaline activity (0.3; 0.2-0.7 nmol/l). Noradrenaline concentration showed a nonsignificant decreasing trend with increasing alfentanil dose and beta endorphin was unchanged. Rigidity was noted in the placebo (n = 2), 10 micrograms/kg (n = 2), and 20 micrograms/kg (n = 5) alfentanil groups, respectively. CONCLUSIONS: Tracheal suction is a painful procedure. The dose of alfentanil required for pain relief (20 micrograms/kg) causes a high incidence of rigidity and thus should be used only with muscle relaxant.     

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.     

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.