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Materials and methods Seven days old male Swiss mice were distributed on three groups: hypoxia (H), maternal separation (MS) and no handling (NH). H group underwent to 10% oxygen during 6 hours/day for 6 days and MS group was maintained in normoxia, but separated from their dams such as H group. When mice completed 3 months old, they were tested on locomotor activity boxes or in plus-maze. The parameters measured were erythrocyte catalase, superoxide dismutase and glutathione peroxidase (GPx) and cerebral catalase. Data were analyzed by one-way ANOVA test and Bonferroni post-hoc test, when appropriated.

We have previously shown that neonatal mice deficient in endothelial nitric oxide synthase (eNOS−/−) are more susceptible to hypoxic inhibition of alveolar and vascular growth. Although eNOS is downregulated, the role of nitric oxide (NO) during recovery after neonatal lung injury is poorly understood. We hypothesized that lung vascular and alveolar growth would remain impaired in eNOS−/− mice during recovery in room air and that NO therapy would augment compensatory lung growth in the eNOS−/− mice during recovery. Mice (1 day old) from heterozygous (eNOS+/−) parents were placed in hypobaric hypoxia (FiO2= 0.16). After 10 days, pups were to recovered in room air (HR group) or inhaled NO (10 parts/million; HiNO group) until 3 wk of age, when lung tissue was collected. Morphometric analysis revealed that the eNOS−/− mice in the HR group had persistently abnormal lung structure compared with eNOS-sufficient (eNOS+/+) mice (increased mean linear intercept and reduced radial alveolar counts, nodal point density, and vessel density). Lung morphology of the eNOS+/− was not different from eNOS+/+. Inhaled NO after neonatal hypoxia stimulated compensatory lung growth in eNOS−/− mice that completely restored normal lung structure. eNOS+/− mice (HR group) had a 2.5-fold increase in lung vascular endothelial growth factor (VEGFR)-2 protein compared with eNOS+/+ ( P < 0.05). eNOS−/− mice (HiNO group) had a 66% increase in lung VEGFR-2 protein compared with eNOS−/− (HR group; P < 0.01). We conclude that deficiency of eNOS leads to a persistent failure of lung growth during recovery from neonatal hypoxia and that, after hypoxia, inhaled NO stimulates alveolar and vascular growth in eNOS−/− mice.

OBJETIVOS: analisar os resultados obstétricos e perinatais de 26 casos de síndrome de aspiração de mecônio (SAM) MÉTODOS: realizou-se revisão dos prontuários de 26 recém-nascidos (RN) com diagnóstico de SAM. Os casos foram estudados em função da média de permanência do RN na UTIN e das principais complicações maternas e neonatais, correlacionando-as entre si. RESULTADOS: dezoito conceptos nasceram no HG-FUCS e 8 fora; no período citado, ocorreram 3.976 nascimentos no HG-FUCS, incidência de SAM de 0,45%. Dos 18 casos estudados, 9 nasceram pela via vaginal; o peso ao nascimento foi >2.500 g em dezesseis casos. Mecônio leve ocorreu em 50%, semelhante ao espesso. O Apgar no 1º minuto foi >7 em 3 casos (16,7%), entre 4 e 6, em 7 casos (38,9%), e entre 0 e 3, em 8 casos (44,4%). No 5º minuto, sete RN permaneceram deprimidos. A principal complicação neonatal foi anoxia (36% dos casos). A taxa de óbito neonatal foi de 7,7%. A internação média na UTIN foi de 19,9 dias. CONCLUSÃO: a SAM constitui grave entidade clínica neonatal, relacionando-se com altas taxas de mortalidade neonatal, mecônio espesso em pelo menos a metade dos casos e nascimento de fetos deprimidos na sua maioria. PURPOSE: to analyze obstetrical and perinatal data in 26 cases of meconium aspiration syndrome (MAS). METHODS: a retrospective review was performed in 26 newborn records diagnosed with meconium aspiration syndrome. Patients were studied emphasizing average days in neonatal intensive care unit and main maternal findings and neonatal complications, correlating them with each other. RESULTS: Eighteen babies were delivered at GH-CSUF and eight out of this hospital. At this time 3,976 deliveries occurred at GH-CSUF, with an incidence of MAS of 0.45%. Nine of 18 babies were born by vaginal delivery; weight was >2,500 g in 16 cases. One-minute Apgar score was >7 in three cases (16.7%), between 4 and 6 in seven cases (38.9%), and between 0 and 3, in eight cases (44.4%). At 5 minutes, seven babies remained

Cilj rada. Sa svrhom da se ustanovi postoji li u rodilištu Opće bolnice Zadar objektivni razlog za povećanje broja carskih rezova, obrađeni su za razdoblje od 1997.–2001. g. (8479 poroda) perinatalni mortalitet i stanje djece po porodu (Apgar zbroj u 1. i 5. min., klinički i laboratorijski znakovi asfiksije, te UZV glave), posebno djece rođene vaginalno, a posebno one rođene carskim rezom. Posebno su obrađeni porodi u stavu zatkom, stanja nakon prethodnog carskog reza, te blizanačka trudnoća. Rezultati. Broj carskih rezova kretao se po godinama otprilike podjednako (6,3–7,79%), prosječno 7,26%. Perinatalni mortalitet pokazivao je veće razlike, tj. od 10,18–3‰ (prosječno 6,73‰). Perinatalni mortalitet djece rođene vaginalno iznosio je 6,02‰, a djece rođene carskim rezom 15,70‰ (t=2,81). Najveći dio perinatalno umrle djece odnosi se na fetalnu smrt. Rani neonatalni mortalitet djece rođene vaginalno iznosio je 2,55‰, a djece rođene carskim rezom 9,47‰ (t=3,12), s tim da je 64% rano neonatalno umrle djece bilo nedonošeno. Vrijednost Apgar zbroja, Objective. In order to determine whether there is an objective reason to increase the number of Cesarean sections in General Hospital Zadar, for the period from 1997–2001 (8479 deliveries) the perinatal mortality and post-born conditions of children (a 1-minute and 5-minute Apgar score, clinical and laboratory signs of asphyxia, head ultrasound) were analyzed. Separate analysis was made of vaginally delivered children and of those delivered by Cesarean section. Breech deliveries, deliveries after previous Cesarean section and twin pregnancies were analyzed too. Results. Annually, the number of Cesarean sections was nearly equal (6.3–7.79%) in average 7.26%. Perinatal mortality indicated wider differences, i.e. 10.18–3.0‰, in average 6.73‰. Perinatal mortality of vaginally delivered children was 6.02‰ and of children delivered by Cesarean section 15.70‰ (t=2,81). The most part of perinatally dead children refers to fetal death. Early neonatal mortality of vaginally delivered children was 2.55‰, and of children delivered by Cesarean section 9.47‰ (t=3.12). The 64% of all early neonatally dead children where delivered as prematures. A 1-minute Apgar score

Background and aims The use of biomarkers is an important strategy for risk stratification for neonates admitted to the NICU after perinatal asphyxia. Total Tau (t-Tau), phosphorylatedTau (p-Tau) and Beta-Amyloid (1–42) (b-A) in CSF, are useful biomarkers in various neurological disorders, such as Alzheimer's. Few, if any, experiments have investigated the possible association between oxidative stress in the neonates and the levels of these proteins. ![Abstract PS-159 Table 1][1] Abstract PS-159 Table 1 ![Abstract PS-159 Table 2][1] Abstract PS-159 Table 2 Objective To study any correlations between the levels of t-Tau, p-Tau, b-A, S100B and NSE and oxidative stress in the newborn pig. Methods Fifty-four newborn piglets, age12–36 h, were included. One control group (n = 6) and 2 experimental groups (n = 24), exposed to global hypoxia (8% O2) until BE reached -15 mmol/l (moderate hypoxia) or -20 mmol/l (severe hypoxia) or BP fell below 20 mmHg. The pigs were observed for 9.5 h. CSF was collected 9.5 h after the intervention. Discussion To our knowledge this is the first study investigating the levels of Tau, p-Tau and b-Amyloid in a neonatal animal model after hypoxia-reoxygenation. The reduced level of CSF b-Amyloid may reflect the death of neurons after neonatal hypoxia. A strategy of measuring several biomarkers should be applied when assessing the prognosisafter perinatal asphyxia. Conclusion These findings show that b-amyloid and S100b are significantly changed in neonatal pigs subjected to hypoxia compared to controls, thus they may be valuable biomarkers after perinatal asphyxia. [1]: pending:yes

Increases in plasma lipids occur during hypoxia in suckling but not in weaned rats and may result from altered hepatic enzyme activity. We exposed rats to 7 days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of age (weaned at day 21). Hypoxia led to an increase in hepatic lipid content in the suckling rat only. Hepatic lipase was decreased to approximately 45% of control in 7-day-old rats exposed to hypoxia but not in hypoxic 35-day-old rats. Hypoxic suckling rats also had a 50% reduction in lactate dehydrogenase activity, whereas transaminase activity and CYP1A and CYP3A protein content were not different between hypoxic and normoxic groups. Additional rats were studied 7 and 14 days after recovery from hypoxic exposure from birth to 7 days of age; hepatic lipase activity had recovered to 85% by 7 days and to 100% by 14 days in the rats previously exposed to hypoxia. Administration of dexamethasone to neonatal rats to simulate the hyperglucocorticoid state found in hypoxic 7-day-old rats led to a moderate decrease ( approximately 75% of control) in hepatic lipases. Developmentally, in the normoxic state, hepatic lipases increased rapidly after birth and reached levels more than twofold that of the newborn by 7 days of age. Hypoxia delays the maturation of hepatic lipases. We suggest that the decrease in hepatic lipase activity contributes to hyperlipemia in the hypoxic newborn rats.

Objetivo: avaliar a acurácia da percepção materna dos movimentos fetais (PMMF) na predição de alguns resultados perinatais em gestantes diabéticas. Métodos: análise retrospectiva de 209 gestantes diabéticas atendidas no Centro de Atenção Integral à Saúde da Mulher (CAISM), entre junho de 1988 e maio de 1996, que tinham registro de PMMF dentro dos três dias anteriores ao parto, monitorização eletrônica da freqüência cardíaca fetal intraparto, idade gestacional > ou = 30 semanas, avaliação do recém-nascido (RN) e diagnóstico neonatal. O teste de PMMF foi considerado normal quando a mulher detectou um mínimo de 7 movimentos em 60 minutos. Resultados: a sensibilidade do teste foi de 23 e 29% para Apgar 7 at 5 min and neonatal hypoxia. Conclusions: MPFM is a useful test to identify diabetic women needing fetal evaluation with more complex techniques, given the high NPV, that indicates the capacity to separate the cases where the fetus is in good condition.

Background- Hypoxia during the first week of life can induce neuronal death in vulnerable brain regions usually associated with an impairment of cognitive function that can be detected later in life. The neurobiological changes mediated through neurotransmitters and other signaling molecules associated with neonatal hypoxia are an important aspect in establishing a proper neonatal care. Methods- The present study evaluated total GABA, GABAB receptor alterations, gene expression changes in GABAB receptor and glutamate decarboxylase in the cerebellum and brain stem of hypoxic neonatal rats and the resuscitation groups with glucose, oxygen and epinephrine. Radiolabelled GABA and baclofen were used for receptor studies of GABA and GABAB receptors respectively and Real Time PCR analysis using specific probes for GABAB receptor and GAD mRNA was done for gene expression studies. Results- The adaptive response of the body to hypoxic stress resulted in a reduction in total GABA and GABAB receptors along with decreased GABAB receptor and GAD gene expression in the cerebellum and brain stem. Hypoxic rats supplemented with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GAD. Resuscitation with oxygen alone and epinephrine was less effective in reversing the receptor alterations. Conclusions- Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes in GABA and oxygenation, which helps in encountering hypoxia. The present study suggests that reduction in the GABAB receptors functional regulation during hypoxia plays an important role in central nervous system damage. Resuscitation with glucose alone and glucose and oxygen to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.

112 G-Csf Prevents Long-Term Behavioral Deficits and Brain Injury Following Neonatal Hypoxia-Ischemia in Rats

OUTCOMES: THE INTEROBSERVER VARIABILITY SUNEET CHAUHAN, CHAD KLAUSER, THOMAS WOODRING, MAUREEN SANDERSON, EVERETT MAGANN, JOHN C. MORRISON, Society for Maternal-Fetal Medicine, West Allis, Wisconsin, University of Mississippi Medical Center, Jackson, Mississippi, University of Mississippi Medical Center, Obstetrics & Gynecology, Jackson, Mississippi, University of Texas Health Science Center at Houston, Brownsville, Texas, Naval Medical Center, Obstetrics & Gynecology, Portsmouth, Virginia, University of Mississippi Medical Center, Obstetrics and Gynecology, Jackson, Mississippi OBJECTIVE: The purpose of this study was, among patients with non-reassuring (NR) fetal heart tracings (FHT), determine the interobserver variability (IV) in interpretation of FHT (using the definitions in ACOG practice bulletin on the topic) and the ability to predict 1) patients requiring emergency cesarean delivery (ECD); 2) umbilical arterial [UA] pH 7.00; 3) base excess [BE] -12 mmol/L; and 4) Apgar score [AS] 3 at 5 min. STUDY DESIGN: Five clinicians (1 generalist and 4 MFM), not involved with the care of cohorts, reviewed 100 FHT. Ten tracings with objective evidence of fetal compromise were matched with 9 other FHT from the same time period. The FHT were divided into two phases: an hour prior to periodic decelerations and, if applicable, the hour before delivery. Weighted kappa coefficients (WKC) were calculated to assess inter-observer variability for episodic decelerations, whether the FHT is reassuring or uninterruptible, and the four outcomes. Spearman correlation coefficients (SCC) were calculated to assess the correlation between predicted and actual outcomes overall and by observer. RESULTS: Among 100 cohorts, 46% had CD for NR FHT; 2%, UApH 7.00 (acidosis); BE 12 in 14% and 3% had AS 3 at 5 min (low AS). The WKC for classifying the FHT as being reassuring in early labor was 0.12 and before delivery 0.15. The WKC for the 5 clinicians for predicting ECD was 0.26; for acidosis, 0.21; for abnormal base excess 0.16, and; for low AS at 5 min, 0.17. The SCC for each observer was 0.005 to 0.21 for ECD; for UApH, 0.01 to 0.46; for BE 0.03 to 0.29 and; for low AS 0.0 to 0.31. In the prediction of the UApH 7.00, three observers differed significantly (P 0.05) from one of the clinicians. The SCC range from 0.10 to 0.19 for the 4 outcomes. CONCLUSION: The reproducibility of and utility of FHT as a predictor of neonatal hypoxia is questionable because, there is a poor agreement among clinicians regarding interpretation of FHT and they cannot reliably identify newborn with hypoxia.

Mild/Moderate Neonatal Hypoxia(MMNH) with Normal Blood Glucose Levels(BGL) Influence in Rats Maze Performance(MP). 49

Noradrenergic (NA) neurons in the brainstem are assumed to be involved in arousal mechanisms (locus coeruleus or A6) and cardio-respiratory control(nucl. tr. solitarius or A2). We have earlier reported an acute depression of NA turnover in newborn rats exposed to hypoxia (Acta Physiol.Scand.1992.144:433) The aim was now to investigate the acute effect of perinatal asphyxia and the long-term effects of chronic hypoxia on NA-turnover in the rat brain.

DEXTROMETHORPHAN (DM) AMELIORATES EFFECTS OF NEONATAL HYPOXIA ON BRAIN MORPHOLOGY AND SEIZURE THRESHOLD IN RATS. • 2239

Fetal and/or neonatal malnutrition has been reported to cause lifelong changes of the control of blood pressure and glucose control etc. according to Barker et al (Lancet 341:938-941.1993). The aim of the present study was to investigate whether chronic neonatal hypoxia could cause longterm changes of catecholamine (CA) turnover in the sympatho-adrenal system and the carotid bodies One day old male pups were exposed with their dams to mild hypoxia (10% O2) for 6 days and thereafter grew up under normoxia until sacrifice. Normoxic control and neonatal hypoxic rats were examined at 3 or 8 weeks with regard to CA turnover. The levels and turnover rates of dopamine (DA), norepinephrine(NE) were determined in sympathetic ganglia and their main target organs, the adrenals and the carotid bodies. After exposure to neonatal hypoxia the turnover rates of NE in the superior cervical, stellate and coeliac-mesenteric ganglia were significantly (p

AIM:We studied the effect of moderate hypoxia on nuclei/cytoplasm index at different levels of the parietal cortex of the rat at 1 month of age. MATERIAL AND METHODS: Eight brains coming from 2 litters of 1 month-old rats submitted to a neonatal hypoxia (Fi O2=10%) and standardized to 10 animals per litter were processed and stained with Nissl method. Random slide of each case was selected and studied by digitalized microscopic pictures of 70 μm width and all the cortical structures depth. Measurements of main nuclei and cytoplasm diameters of neurons in different layers were taken and results compared with 6 controls brought up in the same circumstances. Mann-Whitney test was used to comparisons. CONCLUSIONS: Nuclei/cytoplasm index of pyramidal cells was significantly greater among hypoxic than in control animals. We can conclude that slight hypoxic expositions can produce alterations in the rat neurons morphology in later stages of the development.

Sligth hypoxic-ischemic perinatal event can originated scare problems in later netirodevelopment, The aim of this job is to show the effects of two levels of hypoxia in a maze test resolution. Three groups of newborn Wistar rats were placed in an exposure chamber. They were keep in their mothers' cages till weaning (day 21). Days 25 and 26 they were submitted to maze trials. After fasting from day 28 until 30th, they were submitted again to a new maze trial. The variable validating the anirrals' behaviour was the number of squares crossed in the maze resolution (SC). Results and statistical analisys (ANOVA) are as follows: V5 group obtained a best profile in the learning capacity than V10 group. Number of errors (SC) decreased dramatically in V5 as happend wiht SH group, while V10 remained the same level of the first trial. However we are not sure if these effects can be exclusively related to the absence of presumed handicap rats who died, or to any other genetic/environmental factor.

Our current ability to predict long-term neurologic outcome based upon intrapartum information is very limited. Adding information on the neurologic state during the first days of life adds powerfully to the ability to predict outcome. An understanding of causation requires consideration of antepartum factors, since many characteristics commonly labelled as indicators of "neonatal hypoxia" may be the first evidence in the infant of abnormality that predated labor.

Forty-six neonates with hypoxemia were treated with tolazoline, a pulmonary vasodilator, within the first two days of life. Eight of ten (80%) infants without apparent lung disease responded with a mean increase in PaO2 of 116 torr within one hour of beginning tolazoline infusions. One of the responding infants and two nonresponders died. Thirty-six additional infants with a variety of pulmonary disorders had severe hypoxemia which was refractory to mechanical ventilation. Twenty-one (58%) responded with a mean increase in PaO2 of 130 torr within one hour after beginning tolazoline and 13 (62%) of these survived. Fifteen patients had little or no improvement in PaO2 following tolazoline and only three (20%) of these infants survived. Responders could not be distinguished from nonresponders by clinical or laboratory features prior to therapy with tolazoline. Fourteen infants experienced complications possibly related to tolazoline.

As a consequence of obstetric complications, neonatal hypoxia has been discussed as an environmental factor in the pathophysiology of schizophrenia. However, the biological consequences of hypoxia are unclear. The neurodevelopmental hypothesis of schizophrenia suggests that the onset of abnormal brain development and neuropathology occurs perinatally, whereas symptoms of the disease appear in early adulthood. In our animal model of chronic neonatal hypoxia, we have detected behavioral alterations resembling those known from schizophrenia. Disturbances in cell proliferation possibly contribute to the pathophysiology of this disease. In the present study, we used postnatal rats to investigate cell proliferation in several brain areas following neonatal hypoxia. Rats were repeatedly exposed to hypoxia (89 % N(2), 11 % O(2)) from postnatal day (PD) 4-8. We then evaluated cell proliferation on PD 13 and 39, respectively. These investigations were performed in the anterior cingulate cortex (ACC), caudate-putamen (CPU), dentate gyrus, and subventricular zone. Rats exposed to hypoxia exhibited increased cell proliferation in the ACC at PD 13, normalizing at PD 39. In other brain regions, no alterations have been detected. Additionally, hypoxia-treated rats showed decreased CPU volume at PD 13. The results of the present study on the one hand support the assumption of chronic hypoxia influencing transient cell proliferation in the ACC, and on the other hand reveal normalization during ageing.

Previous studies have shown that severe neonatal asphyxia and hypoxia lead to a redistribution of cerebral blood flow (CBF) with a preferential perfusion of the brain stem. The present study shows that this mechanism is operative also in moderately hypoxic newborn lambs (oxygen saturation 32.7-65.2) with a threshold of about 25% reduction in oxygen saturation. In hypoxia, the mean increase in total CBF, brain stem and telencephalic blood flow was 44%, 68% and 43%, respectively (five lambs). We found that naloxone reverses this redistribution, and that the effects of naloxone on telencephalic perfusion and cerebral metabolic rate of oxygen (CMRO2) were proportional. In hypoxia + naloxone (1 mg/kg), a further increase in total CBF, brain stem, and telencephalic blood flow of 30%, 7% and 31% was noted. We therefore suggest that the redistribution of CBF is an important opioid-mediated homeostatic mechanism, which diminishes the metabolic requirements of the newer part of the brain in hypoxia and allows a preferential perfusion of the vital structures of the brain stem.

The behavioral performance of rats subjected in the neonatal period to hypoxia-ischemia at either 37 degrees C or 21 degrees C was compared to that of sham-ligated animals. Performance on complex motor tests was significantly delayed only in the hypoxic-ischemic 37 degrees C rats. However, cognitive testing disclosed significant delay of spatial learning in animals subjected to hypoxia-ischemia at 21 degrees C and those with gross infarction at 37 degrees C. There was enhanced avoidance learning in the animals with gross infarction in the hypoxia-ischemia 37 degrees C group. Hypoxic-ischemic damage in the neonatal rat at 37 degrees C results in transient delay of complex motor skills, but longer lasting cognitive changes. Hypoxia-ischemia during hypothermia produces no motor deficits, although there may be similar alterations in learning.

Hypoxanthine levels were determined in both venous and arterial cord blood of 42 neonates. Two methods were compared, a PO2 electrode determination and an HPLC (high-pressure liquid chromatography) method. A good correlation was found between the two methods. However, the HPLC method was more sensitive, more reproducible and easier to perform. Hypoxanthine levels in the umbilical artery were found to be higher than in the vein. A significant negative correlation between pH and hypoxanthine level was established. The studies showed that plasma hypoxanthine levels by themselves did not provide an absolute diagnosis of intrauterine hypoxia.

Sinusoidal heart rate traces were detected in 8 patients, 6 of whom died; the 2 survivors showed evidence of gross cerebral damage. It is felt that the origin of the sinusoidal curve is probably central and reflects loss of central control of heart rate.

Hypoxia in the neonate releases catecholamines from the adrenal medulla, a response which is necessary to survive. This study examines whether a similar dependence exists for the ability of brain and heart tissue to recover from hypoxia-induced damage, as assessed by measurements of ornithine decarboxylase (ODC) activity. Hypoxia at either 1 day or 8 days of age produced a subsequent elevation of brain ODC which persisted for 1 week, a pattern known to be associated with recovery from tissue damage and delayed cellular maturation. Pretreatment of the rats with phenoxybenzamine, an alpha-receptor blocking agent, resulted in attenuation of the long-term ODC response, but did not interfere with effects on the enzyme during the hypoxia itself. In the heart, hypoxia at 8 days of age displayed similar effects, with long-term ODC elevations which were attenuated by phenoxybenzamine. Hypoxia at 1 day of age also produced long-term heart ODC stimulation, but in this case the effect was exacerbated by phenoxybenzamine, an effect consistent with the greater dependence of cardiac tissue on alpha-receptor-mediated responses to hypoxia at that age. These results suggest that alpha-receptor stimulation by catecholamines released during neonatal hypoxia play a role in the metabolic adjustment of brain and heart tissue to damage and may aid in subsequent recovery.

Periventricular areas of decreased attenuation coefficient were demonstrated by computed tomography (CT) in two infants with neurological involvement after episodes of neonatal hypoxia. This CT finding is related to anoxic periventricular leukomalacia, which is well documented in the literature. Follow-up CT scans in our two patients demonstrated reversibility of the white matter changes.