The Effect of Probabilistic Context on Implicit Temporal Expectations in Down Syndrome.

One of the most important sources of predictability that human beings can exploit to create an internal representation of the external environment is the ability to implicitly build up subjective statistics of events' temporal structure and, consequently, use this knowledge to prepare for future actions. Stimulus expectancy can be subjectively shaped by hierarchically nested sources of prediction, capitalizing on either local or global probabilistic rules. In order to better understand the nature of local-global proactive motor control in Down Syndrome, in the present study a group of participants with Down Syndrome (DS group; n = 28; mean age 29.5 ± 13 years; range 10-54) and a group of typically developing participants matched by either gender or mental age (TD-MA group; n = 28; 5.6 ± 1 years; range 4-8) were administered a novel motor preparation task, defined as the Dynamic Temporal Prediction (DTP) task. In the DTP, the temporal preparation to imperative stimuli is implicitly shaped by the local increase of expectancy. This is manipulated trial-by-trial as a function of the preparatory foreperiod interval (Stimulus-Onset Asynchrony or SOA). In addition, temporal preparation can be also implicitly adjusted as a function of global predictive context, so that a block-wise SOA-distribution bias toward a given preparatory interval might determine a high-order source of expectancy, with functional consequences on proactive motor control adjustment. Results showed that in both groups motor preparation was biased by temporal expectancy when this was locally manipulated within-trials. By contrast, only the TD-MA group was sensitive to global rule changes: only in this cohort was behavioral performance overall impacted by the SOA probabilistic distribution manipulated between-blocks. The evidence of a local-global dissociation in DS suggests that the use of flexible cognitive mechanisms to implicitly extract high-order probabilistic rules in order to build-up an internal model of the temporal properties of events is disrupted in this developmental disorder. Moreover, since the content of the information to be processed in the DTP task was neither verbal nor spatial, we suggest that atypical global processing in Down Syndrome is a domain-general rather than specific aspect characterizing the cognitive profile of this population.

Oxidative stress in twin neonates is influenced by birth weight and weight discordance.

OBJECTIVES: To evaluate the extent of oxidative stress in neonates born from multiple gestation pregnancies who are at high risk of prematurity and growth abnormalities. DESIGN AND METHODS: Blood samples were collected from umbilical cord of 72 twins, born at gestational age of 28-38 weeks, and 20 consecutive control singletons. Oxidative stress parameters (15-F(2t)-isoprostane, a marker of lipid peroxidation, and total antioxidant capacity, tAOC), were measured in cord plasma. RESULTS: Levels of 15-F(2t)-isoprostane showed a moderate negative correlation with birth weight and were higher in small co-twins of discordant pairs; tAOC was positively correlated with birth weight but no significant difference was found between co-twins. CONCLUSIONS: Oxidative stress levels in twins are mainly influenced by birth weight and weight discordance. We suggest that evaluation of cord blood 15-F(2t)-isoprostane might be of clinical value as maker of pre- and perinatal distress in twinning.

Auditory processing during sleep in preterm infants: An event related potential study.

Auditory processing during sleep was investigated in premature infants by auditory event related potentials (AERPs). Twenty-six premature infants (mean GA 30 week- range 25-35) admitted to a neonatal intensive care unit were studied, prior to discharge, in active and quiet sleep at a mean post-conceptional age of 35 weeks. Infant state was determined by behavioral observation according to standard criteria. An auditory odd-ball paradigm was used with frequently occurring 'standard' tones at 1000Hz and infrequent 'deviant' tones at 2000Hz. Waveforms were recorded at Fz, Cz, Pz, T3 and T4 scalp locations. Measurements were performed in 18 patients because 8 preterm infants were excluded since they had less than the required artifact-free deviant trials in each sleep state. The responses to standard tones were equally recorded in both active and quiet sleep, but auditory responses to deviant tones consisting of an increased frontal negativity in the time period from 200 to 300ms after the stimulus were recorded only in active sleep. A significant effect of electrode placement, for frontal location by sleep condition and sleep condition by 50ms time windows was shown by repeated measures analyses of variance. The significance of these findings on evoked potential methodology in preterm infants admitted to neonatal intensive care unit is discussed.

Neurodevelopmental outcome in preterm histological chorioamnionitis.

The role of histological chorioamnionitis in neonatal neurological outcome is not yet fully understood. The present study aimed to assess the neurodevelopmental outcome of preterm babies born after pregnancy complicated by histological chorioamnionitis. Clinical data were prospectively collected for consecutive premature neonates born before 32 weeks of gestation, admitted to Neonatal Intensive Care Unit of Padua University from January 1998 to December 2001. Placental histology was performed. Outcome at 18 months of corrected age was evaluated by a standardized postal parental questionnaire. Among 104 placentas examined, 41 (39.4%) were diagnosed with histological chorioamnionitis. Reply to the postal questionnaire was available from 76.1% of the families. The relative risk of disability in vision, hearing, speech and motor development was higher in the histological chorioamnionitis than in the non-histological chorioamnionitis group, with statistical significance in speech delay (relative risk 2.37; 95% confidence interval: 1.33-4.22) and hearing loss (relative risk 2.76; 95% confidence interval:1.64-4,64). To our knowledge this is the first report suggesting preterm histological chorioamnionitis as a possible risk factor for hearing loss and speech delay.

High prevalence of inherited thrombophilia in 'presumed peri-neonatal' ischemic stroke.

The aim of this study was to assess the prevalence of inherited thrombophilia in 'peri-neonatal arterial ischemic stroke' (AIS), and its possible correlation with type of stroke and long-term neurological outcome. A cohort of twenty-four infants affected by AIS were analysed for risk factors, clinical and neuroradiological features, coagulation and thrombophilia profile and outcome. Two subgroups were considered, based on clinical presentation: infants symptomatic in the neonatal period, acute AIS (aAIS) and those with a delayed presentation (presumed peri-neonatal onset, pAIS). The mean follow-up on patients was 3 yr and 1 month (range 1-15 yr). Inherited thrombophilia, consisting of factor V Leiden and prothrombin G20210A mutations, protein C and/or protein S deficiencies, was detected in 28.6%. A significantly higher prevalence of inherited thrombophilia was observed in infants with pAIS compared with aAIS (Fisher's exact test, P = 0.011). Infants with pAIS had a significantly worse neurological outcome with respect to aAIS (Fisher's exact test, P = 0.014). Inherited thrombophilia was significantly higher in patients with a poor neurological outcome (Fisher's exact test P = 0.002). Although the clinical presentation (aAIS vs. pAIS) was associated with future neurological disabilities, it is the thrombophilia but not the clinical presentation, which remains the only significant prognostic factor in the logistic regression analysis. Although preliminary, these data suggest an association of unfavourable neurological outcome and inherited prothrombotic defects in neonatal AIS. The higher prevalence of inherited thrombophilia identified in pAIS and the worse neurological outcome encourage further investigations in population-based studies.

Plasma levels of 15-F(2t)-isoprostane in newborn infants are affected by mode of delivery.

OBJECTIVE: To investigate how the mode of delivery affects the level oxidative stress in newborns. DESIGN AND METHODS: 15-F(2t)-isoprostane, as index of oxidative stress, was measured in umbilical cord plasma samples from 37 infants born after vaginal delivery or caesarian section, using specific immuno-affinity extraction and immunoassay. RESULTS: 15-F(2t)-isoprostane levels were higher in infants born after vaginal delivery (n=18) compared to those delivered by elective caesarian section (n=19). CONCLUSIONS: 15-F(2t)-isoprostane is a sensitive biomarker of fetal oxidative stress during labor.

Acute necrotizing encephalopathy: combined therapy and favorable outcome in a new case.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare disease characterized by multiple, symmetrical brain lesions, affecting thalami, brainstem tegmentum, and cerebellar medulla; more inconstantly, other structures are involved, i.e., internal capsules, posterolateral putamen, and deep periventricular white matter. FEATURES: The clinical picture consists of rapidly deteriorating acute monophasic encephalopathy preceded by prodromal febrile illness; the symptoms include hyperpyrexia, convulsions, recurrent vomiting, and coma within 24 h. PROGNOSIS: The outcome is usually poor and approximately 70% of the patients die within a few days from the onset of fever. There is no specific therapy for ANE but, in some patients, the clinical status improved with steroid treatment.

Endothelin receptor A -231 G>A polymorphism: no linkage to primary pediatric headache.

OBJECTIVE: To assess whether the biallelic -231 G>A polymorphism of the endothelin type A receptor (EDNRA) gene, previously shown to be a marker of increased risk for developing migraine, has a role in the susceptibility to primary pediatric headache. BACKGROUND: Several studies suggest that endothelin has a role in migraine. A recent association study has shown that the biallelic -231 G>A polymorphism of the EDNRA gene is associated to migraine in an elderly population. METHODS: A total of 126 consecutive unrelated pediatric patients affected by primary headache, classified according to the International Headache Society criteria in migraine (migraine with aura, n = 3; migraine without aura, n = 80), and tension-type headache (episodic tension-type headache, n = 36; chronic tension-type headache, n = 7) patients, were recruited to the study. Sixty-seven healthy blood donors were used as a control group. Genomic DNA was extracted from buccal swabs or blood samples and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the above-mentioned polymorphism. Allele and genotype frequencies for primary headache patients were analyzed in comparison with the control group. RESULTS: No significant differences were found in the distribution of the EDNRA -231 G>A polymorphic variant when considering both genotype (migraine chi2 = 2.78, P = .25; tension-type headache chi2 = 3.58, P = .17) and allelic frequencies (migraine chi2 = 1.48, P = .22; tension-type headache chi2 = 0.39, P = .56). Furthermore, no significant genotype-related difference was found in relation to clinical features, such as age at onset, frequency, and length of the attacks. CONCLUSIONS: Our study shows that the -231 G>A polymorphism in the EDNRA gene is neither associated with primary juvenile headache nor significantly correlated with main clinical features characteristic of the headache pathology in pediatric settings.

Genetic risk factors in primary paediatric versus adult headache: complexities and problematics.

Numerous candidate genes for migraine have been proposed on the basis of their possible functional role in its pathogenesis. Genetic polymorphisms have been evaluated in association studies, some of which have been suggested to be susceptibility markers for adult migraine. To date, however, none of the identified polymorphisms in adult migraine susceptibility have been investigated in children, raising the possibility that they may not be necessarily involved in paediatric migraine susceptibility. This paper reviews studies of the genetic basis of migraine and summarises our experience in genetic association studies in primary paediatric headache susceptibility.

The effect of pre-eclampsia on the levels of coagulation and fibrinolysis factors in umbilical cord blood of newborns.

The effect of pre-eclampsia on coagulation and fibrinolysis in newborns is still under investigation. We have evaluated several coagulation and fibrinolysis parameters in umbilical cord blood of 20 newborns from pre-eclamptic women and of 40 newborns from normotensive women with similar gestational age. Additionally, the presence of factor V Leiden and prothrombin G20210A mutation in cord blood has been assessed. Neonates from pre-eclamptic women exhibited significantly lower birth weight (2.48 +/- 0.92 versus 2.88 +/- 0.68 kg, P < 0.05) and were more frequently admitted to the neonatal intensive care unit (45 versus 20%, P < 0.01) as compared with neonates from normotensive women. Cord blood protein C antigen and activated protein C resistance mean levels were slightly higher in the group of neonates from pre-eclamptic mothers. Fibrinogen levels were lower in this group as compared with control newborns (132.17 +/- 46.97 versus 156.08 +/- 49.58 mg%, P < 0.02), and unrelated to birth weight. No significant differences between cases and controls were found in plasminogen activator inhibitor-1 or tissue plasminogen activator cord blood levels. Heterozygous prothrombin 20210A was found in three newborns from normotensive mothers, whereas no factor V Leiden mutation was found in either group. In conclusion, pre-eclampsia seems to have only mild effects on coagulation and fibrinolytic factors in the cord blood of newborns. Since no excess of common polymorphisms predisposing to thrombosis was found in newborns from pre-eclamptic mothers, it is unlikely that the carriership status of these genetic defects of newborns influences the adverse pregnancy/neonatal outcomes.

Effect of delivery modalities on the physiologic inhibition system of coagulation of the neonate.

The perinatal period is associated with an increased incidence of thromboembolic complications, which may occur in both the maternal and fetal circulation in otherwise normal and healthy adults and fetuses, and this may be related to the activation of the coagulation system at the time of parturition. The risk of these complications is generally much higher in neonates, who have decreased activity of the physiologic inhibition system of coagulation (PISC), including protein C, protein S and antithrombin, in comparison with adults. Therefore, any additional obstetric iatrogenic factors could predispose the neonate to an increased risk of thromboembolic complications. The aim of this study was to evaluate the influence of modality of delivery (spontaneous vaginal delivery vs. elective caesarian section) on the neonatal PISC factor (protein C, protein S and antithrombin) levels and the fibrinolytic system (plasminogen and fibrinogen levels). We studied 41 consecutive healthy newborns, 18 delivered vaginally (mean gestational age 39.7 +/- 0.8) and 23 by elective caesarian section (mean gestational age 38.5 +/- 0.7). Plasma samples were collected from the umbilical cord at birth. AT activity, protein C antigen and activity, total and free protein S antigen, fibrinogen concentration and plasminogen activity were tested. Among PISC factors studied in cord blood of infants born after vaginal delivery, protein C antigen levels and antithrombin activity were statistically higher (41.3 +/- 9.4 vs. 33.9 +/- 7.2 and 58.5 +/- 10.0 vs. 48.4 +/- 12.7, respectively; P<.01), while free protein S was significantly lower (36.8 +/- 11.6 vs. 46.4 +/- 12.5; P<.05) than in newborns delivered by caesarian section. Cord blood plasminogen and fibrinogen were elevated in vaginally delivered neonates in comparison to those delivered by caesarian section, but the difference was not statistically significant. Our data show that the labor stress of vaginal delivery may play a role in influencing the levels of some PISC factors in the cord blood of full-term neonates. In newborns with coagulation disorders, separate reference ranges in coagulation screening tests should be possibly needed depending on the delivery modality.