Levels and plasma distribution of free and C4b-BP-bound protein S in human fetuses and full-term newborns

Levels and plasma distribution of protein S were measured on umbilical cord plasmas from 25 normal full-term newborns and 25 normal fetuses which were between 20 and 31 weeks of gestation. Fetal blood samples were obtained by direct puncture of the umbilical vein under high resolution real-time ultrasound. Total and Free protein S levels were found to be lower in all fetuses and newborns as compared to normal adults. The calculated ratio Total protein S/Free protein S and crossed immunoelectrophoresis patterns indicate that protein S circulates essentially in the free form in fetuses and newborns. These data may be explained by the low levels of C4b-binding protein observed at these stages of development.     

Relevance of platelet serotonin and plasma tryptophan concentration in normal pregnant women and newborns to early child psychiatry

Dysfunctions of the serotonergic system are implicated in psychiatric disorders, and there is evidence that a familial element may be significant in childhood autism. The concentrations of platelet 5-HT and free and total plasma tryptophan were determined in healthy pregnant women at each month of pregnancy and, at delivery, in both maternal and umbilical cord blood. A significant rise in the level of platelet 5-HT occured during month 3 and 4 followed by a retum to normal from month 5 until the delivery. The level of total plasma tryptophan remained equal to that in normal healthy non pregnant women until the 6th month. By month 7, it had decreased significantly and remained low until the month 9. At delivery the level fell significantly by –41%. The concentration of free tryptophan varied widely from one month to another but there was a trend towards a progressive increase from month 1 to 9, and at delivery the level returned to basal values. The concentration of 5-HT in the umbilical cord blood was about half that of the maternal blood. Inversely the concentrations of both free and total plasma tryptophan in the umbilical cord blood were nearly twice that of the maternal blood.

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Zusammenfassung Dysfunktionen des serotoninergen Systems werden bei verschiedenen psychiatrischen Störungen angenommen, wobei es Hinweise für eine familiäre Komponente im Rahmen des kindlichen Autismus gibt. Die Konzentrationen der 5-Hydroxyindolessigsäure in Blutplättchen und des Tryptophans (freie und Gesamtplasmakonzentrationen) wurden in gesunden schwangeren Frauen sowohl im mütterlichen Blut als auch im Nabelschnurblut in jedem Schwangerschaftsmonat und bei der Geburt bestimmt. Ein signifikanter Anstieg der Konzentration der 5-Hydroxyindolessigsäure in Blutplättchen ereignete sich zwischen Mens III und IV, und von Mens V ab an bis zur Geburt normalisierte sich die Konzentration. Der Gesamtplasmaspiegel von Tryptophan glich dem in gesunden nicht-schwangeren Frauen bis zu Mens VI, in Mens VII war er signifikant abgefallen und blieb bis zur Mens IX niedrig. Zum Geburtstermin fiel der Spiegel signifikant um 41%. Die Konzentration des freien Tryptophans zeigte von Monat zu Monat deutliche Schwankungen, wobei es einen Trend in Richtung eines kontinuierlichen Anstiegs von Mens I–IX gab. Zum Termin fiel der Spiegel auf die basalen Werte ab. Die Konzentration der 5-Hydroxyindolessigsäure im Nabelschnurblut betrug ca. die Hälfte derer im maternalen Blut. Umgekehrt waren die Konzentrationen sowohl des freien als auch Gesamtplasmatryptophans im Nabelschnurblut ca. doppelt so hoch wie im maternalen Blut.

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Résumé Le système sérotonergique semble impliqué dans les psychoses infantiles précoces, et, dans la mesure où une prévalence familiale existe pour ces affections, il nous a paru intéressant de déterminer un profil normal de la sérotonine (5-HT) plaquettaire et du tryptophane au cours de la gestation. Ceci dans le but de puvoir interpréter des résultats trouvés pendant la grossesse de femmes déjà mères d'un enfant psychotique. Nous avons déterminé les concentrations en 5-HT plaquettaire et en tryptophane plasmatique total et libre chez des femmes enceintes témoins à chaque mois de grossesse et, à l'accouchement, dans le sang maternel et dans le sang du cordon. La concentration en 5-HT plaquettaire augmente significativement aux 3ème et 4ème mois puis revient à la normale à partir du 5ème mois jusqu'à l'accouchement. Le tryptophane total est normal jusqu'au 6ème mois, il diminue significativement au 7ème mois et reste bas jusqu'au 9ème mois. A l'accouchement, il s'effondre (–41%). Le tryptophane libre varie beaucoup d'un mois à l'autre, il augmente progressivement du début à la fin de la grossesse, à l'accouchement par contre, il est normal. Dans le sang du cordon, la concentration en 5-HT est environ la moitié de celle du sang maternel, le tryptophane total et le tryptophane libre environ deux fois plus élevés.

     

EEG and ischemic stroke in full-term newborns]

The aims of this study were to describe EEG anomalies in unilateral neonatal ischemic stroke without hypoxic-ischemic encephalopathy, and to determine possible links between these abnormalities and long-term outcome. In 6 full-term newborns without severe fetal distress ischemic stroke was confirmed by computed tomography and/or magnetic resonance imaging. Twenty EEGs were recorded during the neonatal period, 5 in acute stage and 15 later. The duration of the follow-up ranged from 3 to 9 years. All newborns developed unilateral clonic seizures, right-sided (5 cases) or left-sided (1 case); seizures began between 14 and 48 h of life. At follow-up, 3 children were normal at 2 and 6 years of age, while the 3 others had sequelae: epilepsy at 9 years of age in one, and unilateral mild cerebral palsy in the 2 others (3 and 4 years of age), with behavioral problems in one of them. Critical EEG discharges, rhythmic sharp waves and/or slow waves were recorded on the injured side. Abnormalities of interictal activity were excess of alpha or theta rhythms, transitory EEG discontinuity or low voltage. The 2 children with cerebral palsy had numerous unilateral post-ictal positive rolandic slow sharp waves (PRSSWs), which were similar to the positive rolandic sharp waves of premature infants; the child with behavioral problems had numerous positive left-sided temporal fast sharp waves. PRSSWs could be associated with contralateral motor sequelae, while positive left temporal fast sharp waves were associated with long term behavioral problems. These findings may be used for future prospective studies aimed at specifying the relation between EEG abnormalities and long-term outcome.     

The orbicularis oculi reflexes in healthy premature and full-term newborns

Blink reflexes were evoked both by mechanical tapping and electrical current delivered to the skin of the periorbital region in 62 healthy babies distributed in 2 groups: 29 full-term newborns and 33 prematures. The electrical activity of the orbicularis oculi muscle was recorded by means of bipolar surface electrodes in all cases. Both ipsilateral R1 and R2 electrically evoked responses were obtained. Occasionally we also observed a late R3 ipsilateral response. The R2 contralateral electrically evoked response was never observed in premature babies; it was present in about 80% of the full-term newborns. The R1 recovery curves obtained by delivering two successive shocks are similar in our two groups of babies to those observed in adults. The R1 latency decreases from 18 msec (27 weeks of post-conceptional age) to 12.4 msec (37 weeks). The average value for the full-term newborns was 12.1 +/- 1.1 msec. Whatever the age mechanical stimulation evokes bilateral R1, R2 and occasionally R3 responses. The existence of central crossed connections is possible. The maturation of the blink reflex occurs essentially during the last months of pregnancy. Indeed the R1 latency measured in full-term newborns is similar to that given for adults.     

Interhemispheric synchrony in the EEGs of full-term newborns.

Cross correlations between 4 homologous pairs of ear-reference derivations were calculated for 45-sec digitized samples of typical active and quiet sleep in 19 selected normal newborns at 21--70 h after term birth. Repeat recordings were obtained in 9 subjects 24 h after the original recordings and another set of cross correlations was calculated. For comparison, similar recordings were obtained from 4 asymptomatic young adults and cross correlations were calculated for 45-sec samples of typical stage 4 and stage REM sleep and for stage W both before and after sleep. Mean cross-correlation coefficients at zero time lag were generally higher for the adult sleep data than for the newborn data, but the differences were smaller than had been anticipated. The coefficients for active sleep data in the newborns were higher than for quiet sleep data, while in the adults the coefficients were higher for stage 4 than for stage REM. Coefficients were higher for convexity derivations than for temporal derivations in both newborns and adults. A review of the small available literature suggests that recording and analysis techniques may be significant variables determining the results obtained in such studies. The cross-correlation method of measuring interhemispheric synchrony may prove useful in identifying brain disorders in the postnatal period.     

Sex and ear differences of brain-stem acoustic evoked potentials in a sample of normal full-term newborns. Normative study

The present paper reports a normative study of the BAEPs recorded from 80 normal full-term newborns by using a rarefaction click at 70, 60, 40, 20 dB HL. Positive, negative peaks and the relative amplitudes were measured. Means, standard deviations and 95% and 99% confidence limits were calculated for each component, for positive and negative IPLs and amplitude ratios. A normality test distribution showed that each component had normal distribution except for wave PIII at 70 dB and at 60 dB HL because of its index of kurtosis and for IPLs PII-PIII and NII-NIII at 70 and 60 dB HL. MLRA was performed and significant statistical differences were found for sex, ears and intensities. Females had the latencies of waves PIII, PIV, PV, NII and NIV shorter than males. The BAEPs obtained from the left ear had shorter latencies for positive and negative peaks. Latencies, amplitude and morphology of the BAEPs vary with variations of the intensity. The IPLs PII-PV, PIII-PV and PIV-PV were not affected by changes of intensity.     

妊娠合并中枢神经细胞瘤足月顺产一例

患者 女性,22岁,宫内妊娠22周,因入院前2d夜间睡眠时癫痫全面强直一阵挛发作于2005年6月1日入院.     

Nonlinear EEG analysis during sleep in premature and full-term newborns.

OBJECTIVE: Recently it has been shown that the adult sleep EEG is mostly determined by high-dimensional, linear dynamics with the exception of the A phase of the cyclic alternating pattern which displays more synchronized nonlinear dynamics. It is not known how these two different types of brain dynamics develop in early life; for this reason the aim of this study was that to extend the nonlinear analysis to the EEG during sleep recorded in premature and full-term newborns. METHODS: EEG epochs were chosen from a total of 24 polygraphic recordings from 14 babies (9 males and 5 females) aged between 33 weeks 3 days and 4 months conceptional age. All subjects were neurologically normal and showed normal psychomotor development at follow-up. A total of 243 artifact-free epochs was chosen during active sleep (AS, 74 total epochs), quiet sleep (QS, 76 total epochs) and indeterminate sleep (IS, 93 total epochs). The dynamic properties of the EEG were assessed by means of the nonlinear cross prediction test which uses 3 different 'model' time series in order to predict nonlinearly the original data set (Pred, Ama, and Tir). Pred is a measure of the predictability of the time series, and Ama and Tir are measures of asymmetry, indicating nonlinear structure. RESULTS: Our results show that the structure of sleep EEG in newborns is significantly different from that of adults, it cannot be distinguished from that of high-dimensional noise in the majority of epochs, and shows a tendency to become nonlinear in nature, mostly during QS, in a small percentage of the epochs analyzed. CONCLUSIONS: These findings can be interpreted as the effect of immature synaptic interconnections between neurons in the newborn brain.     

Sigh-related heart rate changes during sleep in premature and full-term newborns.

The functional linkage in the cardio-respiratory system demands precise coordination of their activity. Sighs provide an opportunity to study the interaction and the maturation of the autonomic nervous system. In 4 groups of normal, sleeping newborns (31 to 41 weeks conceptional age [wCA], 2 to 10 days postnatal age) we investigated heart rate changes caused by sighs by means of polygraphy. In full-term (39-41 wCA) and near-term newborns (37-38 wCA) sighs during quiet sleep (QS) were accompanied by heart rate acceleration (p < 0.01) and thereafter by heart rate deceleration (p < 0.01). During active sleep (AS) only heart rate acceleration (p < 0.01) was observable. In prematures (35-36 wCA) acceleration could be observed in QS (p < 0.01) and AS (p < 0.01) but no deceleration in QS. In prematures of 31-34 wCA no changes during AS and QS could be detected. Body movements caused heart rate acceleration but no heart rate deceleration. In conclusion, it can be hypothesized that heart rate acceleration may be caused by reduced vagotonus initiated by augmented lung volume and movements. Sigh-related changes responsible for heart rate deceleration occur solely during quiet sleep. In prematures of 31-34 wCA these reflexes are not developed.     

Plasma levels of thrombin activatable fibrinolysis inhibitor in normal and preeclamptic pregnant women

To explain the pathogenesis of preeclampsia with coagulation induction or a defective fibrinolysis, various hemostatic parameters were studied and different treatment modalities targeting these parameters were evaluated. Considering the role of TAFI in down-regulation of fibrinolysis, in our study we have investigated whether TAFI contributes to impaired fibrinolysis in patient with preeclampsia. Thirty patients with preeclampsia (mean age +/- SD 25.7 +/- 4.53; range 17-36) and 30 normal pregnant women as control group (mean age +/- SD 28 +/- 5.26; range 21-38) were included in our study. TAFI antigen was determined using an ELISA kit for quantitative measurement. The mean TAFI antigen levels were 12.55 +/- 1.88 microg/ml in patients with preeclampsia and 12.29 +/- 3.0 microg/ml in normal pregnant women. A statistically significant difference was not found between TAFI antigen levels of two groups (p > 0.05). In order to clarify the role of TAFI in the pathogenesis of preeclampsia, in addition to plasma TAFI levels, its synthesis, activation and metabolism should also be evaluated.     

Technical recommendations and interpretation guidelines for electroencephalography for premature and full-term newborns

Electroencephalography (EEG) of neonatal patients is amongst the most valuable diagnostic and prognostic tool. EEG recordings, acquired at the bedside of infants, evaluate brain function and the maturation of premature and extremely premature infants. Strict conditions of acquisition and interpretation must be respected to guarantee the quality of the EEG and ensure its safety for fragile children. This article provides guidance for EEG acquisition including: (1) the required equipment and devices, (2) the modalities of installation and asepsis precautions, and (3) the digital signal acquisition parameters to use during the recording. The fundamental role of a well-trained technician in supervising the EEG recording is emphasized. In parallel to the acquisition recommendations, we present a guideline for EEG interpretation and reporting. The successive steps of EEG interpretation, from reading the EEG to writing the report, are described. The complexity of the EEG signal in neonates makes artefact detection difficult. Thus, we provide an overview of certain characteristic artefacts and detail the methods for eliminating them.     

von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women

ADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and ADAMTS13 activity changes in normal non-pregnant, pregnant and post-delivery women. Fifty-five non-pregnant women, normal blood bank donors, who were not taking contraceptive pills were included as controls. A prospective cross-sectional study of 270 normal pregnant and post-delivery women was carried out. ADAMTS13 activity decreased progressively as from the period of 12-16 weeks up to the end of early puerperium (mean 52%, range 22-89, p < 0.0001), to increase slightly thereafter. Nulliparous presented mildly lower levels of ADAMTS13 activity than parous women (65% vs. 83 %, p = 0.0003), and primigravidae than multigravidae between 6-11 weeks up to 17-23 weeks of pregnancy (69% vs. 80%, p = 0.005). Although in all women the protease levels were the same by blood groups, the O blood group non-pregnant women showed a higher mean of ADAMTS13 activity than those non-O (78% vs. 69%, p = 0.064). Our results suggest that the changing levels of protease activity during pregnancy and puerperium, induced by unidentified mechanisms, could render the peripartum time more vulnerable to developed thrombotic microangiopathies.     

Symmetrical bithalamic hyperdensities in asphyxiated full-term newborns: an early indicator of status marmoratus

Three severely asphyxiated full-term newborns showed tomographic findings of bilateral symmetrical hyperdensities restricted to the thalamic region. All these patients had a strikingly similar poor neurological outcome characterized by dystonia, severe mental retardation and acquired microcephaly. We presume that these bithalamic hyperdensities could be an early predictor of the later status marmoratus.     

Association of protein S p.Pro667Pro dimorphism with plasma protein S levels in normal individuals and patients with inherited protein S deficiency

A dimorphism in PROS1 gene (c.A2,001G, p.Pro667Pro) has been associated with significantly reduced levels of both free and total protein S in carriers of the GG genotype. It is not known how the GG genotype could influence PS levels in normals, whether it could influence the levels of protein S in carriers of mutations in PROS1 gene and whether this genotype acts as an isolated or additive risk factor for venous thrombosis. With this as background, we evaluated the association of p.Pro667Pro dimorphism with free and total protein S centrally measured in a panel of 119 normal controls, 222 individuals with low protein S and 137 individuals with normal PS levels belonging to 76 families with protein S deficiency enrolled in the ProSIT study. Transient expression of recombinant wild type protein S and p.Pro667Pro protein S was performed to evaluate the role of the A to G transition at position 2001 in vitro. The p.Pro667Pro polymorphism was also expressed together with a p.Glu67Ala variant to assess a possible influence on protein S levels in protein S deficient subjects. Free and total protein S levels were significantly lower in normal women. In normal women only was the GG genotype associated with significantly lower free protein S levels in comparison to AA and AG genotypes (P=0.032). No significant influence of GG genotype was observed in patients, either with known mutations or with low protein S levels. These data were confirmed by in vitro transient expression, showing no difference in secretion levels of the p.Pro667Pro variant (even in association with the p.Glu67Ala mutation), compared to the wild type protein S. The genotype in itself was neither a significant risk factor for venous thrombosis nor a risk modifier in patients with known mutations.     

Emotional state and dreams in pregnant women

The aim of this study was to investigate the frequency of recall and the content of dreams during pregnancy, as well as their correlation with socio-demographic, obstetric and physician-patients relationship variables, emotional state and duration of labour. A questionnaire, designed to analyse background characteristics, was given to 290 women in the third trimester of gestation. The psychiatric analysis of anxiety and depression was performed using the Hamilton Rating Scale for Anxiety and the Montgomery-Asberg Depression Rating Scale, while dreams were divided into masochistic and pleasant according to Beck's criteria. Oneiric activity was found to be associated with age>/=35 years, higher family income, higher educational level, and a "satisfactory" physician-patient relationship. Masochistic content was associated with age<35 years, quality of information and frequent thoughts of delivery. Concerning the emotional state, depression levels were higher in women reporting masochistic dreams, while no difference in anxiety levels was found. Labour duration was shorter in the dreamer group and in patients with masochistic dream content. These findings may indicate that, also in pregnancy, the number and the content of dreams are influenced by women's mood and that the evaluation of the oneiric activity might represent a useful tool for clinicians either to investigate the women's emotional state or to predict its repercussions on the course of labour.     

Maternity blues and attachment to children in mothers of full-term normal infants

OBJECTIVE: This study was conducted for evaluating incidence of maternity blues in Japan, in addition to clarifying the relationship between maternity blues and maternal attachment, and the factors involved. METHOD: A questionnaire survey was conducted on 417 mothers having given birth at the Nagoya Daini Red Cross Hospital. The questionnaire consisted of Zung's self-rating depression scale, and a 'postpartum maternal attachment' scale, consisting of subscales on 'core maternal attachment' and 'anxiety regarding children'. The survey was conducted 5.2 days +/-1.46 postpartum. RESULTS: ZSDS scores over 40 amounted to 66.8% of the responses. Analysis of the two scales revealed significant correlation/inverse correlation between 'maternity blues' and 'anxiety regarding children'/ 'core maternal attachment'. Path analysis revealed 'maternity blues' to be influencing 'core maternal attachment' and 'anxiety regarding children'. CONCLUSION: It was found that the incidence of maternity blues may be higher in Japan than was believed previously, and that an intimate association exists between 'maternity blues' and 'postpartum maternal attachment'.     

VEPs in normal full-term and premature neonates: longitudinal versus cross-sectional data

VEPs have been shown to change with CNS maturation in children, yet few studies had documented maturational changes in the premature infant. Using LED goggles, VEPs were studied in 75 neurologically normal infants of 22-42 weeks gestational age (GA) within the first 3 days of life. Twenty of these (22-32 weeks GA) were also followed longitudinally. The 22-23 week GA neonates had no identifiable waves. In all infants greater than 24 weeks a large negative wave is seen with a latency around 300 msec (N300). After 27 weeks GA a late positive wave was present (P400), but with more variable latency and morphology. Between 30 and 35 weeks GA a small positive wave (P200) was seen in over one-third of the neonates; this component was present in all infants greater than 36 weeks GA. The consistency of the N300 across the ages studied suggests that it might arise from the basilar dendrites in the visual cortex, which are well developed by 24 weeks GA and undergo relatively little further development between 24 weeks and term. The P200 is suggested to arise from the apical dendrites which develop in the last trimester, explaining the emergence of P200 after 30 weeks GA. The infants followed longitudinally showed the same components, emerging in the same order, but with more rapid development (particularly of P200) compared to the cross-sectional studies. These data suggest that there are differences in the maturation of the visual system in the extrauterine versus intrauterine environment.