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To study the characteristics of amplitude integrated electroencephalography (aEEG) in preterm infants and changes of maturation with gestational age.aEEG monitoring was done within 3 days of age with domestically produced digital aEEG set (CFM3000). Duration of each recording was at least 4 hours. The continuity, sleep-wake cycle, voltage and bandwidth of all aEEG tracing were analyzed.The percent of continuity background increased from 30% of 28 weeks to 85.7% of 36 weeks (χ(2) = 28.2, P = 0.026); the percent of mature sleep-wake cycle increased from 10% of 28 weeks to 100% of 36 weeks (χ(2) = 192.4, P0.01). Low bound voltage increased with gestational age, from (6.8 ± 1.7) µV (28 w) to 9.7 - 10.1 µV (35 - 36 w) (F = 11.4, P0.01). Bandwidth of the narrow band decreases gradually with gestational age, from 1.45 cm (28 w) to (0.86 ± 0.24) cm (36 w) (F = 8.731, P0.01). The correlation coefficient for continuity, sleep-wake cycle, low bound voltage and bandwidth of narrow band, and total scores were 0.32, 0.81, 0.38, 0.55 and 0.78 respectively (P0.05).The older the gestational age of infants at birth, the more mature the aEEG pattern, manifested as increased continuity and sleep-wake cycle, the higher low bound voltage and more narrowed bandwidth with increased gestational age.

Neonatal lupus erythematosus (NLE) is an uncommon autoimmune disease passively transmitted from the mother in which there is transplacental passage of maternal antibodies. It is often misdiagnosed as intrauterine infection or sepsis. The main purpose of this retrospective study was to improve the understanding of pathogenesis and clinical manifestations of NLE.Clinical manifestations, results of the tests for antinuclear antibodies (ANA), anti-Ro/SSA, anti-La/SSB and anti-dsDNA antibodies in both infants with NLE (8 cases) and their mothers and head ultrasound and CT scans of the infants were analyzed. Follow-up was performed until one and ahalf years of age or all the abnormalities had been resolved.Totally 8 cases (3 males and 5 females) matched the criteria for diagnosis of NLE from September 2003 to February 2006, among whom 4 were small for gestational age and one was born prematurely. Mean gestational age was 38.1 +/- 1.9 weeks, mean birth weight 2 605 +/- 420 grams, mean admission age 22.4 +/- 27.7 days (2 hours-72 days) and mean age of onset 9.4 +/- 12.1 days (0 - 28 days). The common clinical manifestations included cutaneous lupus lesions (8 infants), neural system abnormalities (2 infants) and congenital heart block (2 infants). The skin of the infants exhibited annular, erythematous or desquamative lesions. They all disappeared before 6 months of age. One patient presented with grade III atrioventricular block and was delivered by cesarean section because of "fetal distress". He did not recover at one and a half years follow-up. One infant was hypotonic with delayed neuro-motor development initially and during follow-up with both abnormal neonatal behavioral neurological assessment (NBNA) and image findings. CT showed generalized low density involving periventricular area and deep white matter at one week of age. At the age of one and a half years, he presented with normal mental development index determined by CDCC infant intelligence mensuration. Other abnormal clinical findings included hepatosplenomegaly, anemia, thrombocytopenia, cholestasis and elevated liver enzymes, which were all resolved before 6 months of age. Only 3 mothers of the NLE infants were diagnosed as lupus erythematosus before parturition and only one received partial therapy. At least anti-Ro/SSA antibody or anti-La/SSB antibody or ANA was found in the affected patients. Seven cases had circulating anti-Ro and/or anti-La antibodies in the mothers and in the newborns, while ANA was positive in 7 newborns and in all mothers. All the clinical symptoms except congenital heart block disappeared before 18 months of age. No special intervention was applied.Serum auto-antibodies should be investigated to rule out NLE when there is congenital heart block or rashes or thrombocytopenia presented in a neonate, despite there is no maternal history. Central nervous system abnormalities in NLE are likely to be transient and whether it will cause long term sequelae is uncertain.

A large body of experimental and clinical observations indicates that disturbances in cerebral blood flow (CBF) and impaired cerebrovascular autoregulation are important in the pathogenesis of germinal matrix-intraventricular hemorrhage (GMH-IVH) and periventricular leukomalacia (PVL), the 2 most important forms of brain injury in pretmature infants. Near-infrared spectroscopy (NIRS) has been used recently to estimate CBF in human newborns. The objectives of this study were to evaluate the correlation of NIRS estimations and cerebral blood flow in newborn piglets, which in turn may help provide the ideal NIRS estimation reflecting the changes of cerebral blood flow and cerebrovascular autoregulation.Ten newborn piglets, aged 1 - 3 days, were randomly assigned to one of the following groups: normal control group (n = 6) and hypotension group (n = 4). Hypotension was induced by withdrawing blood from an arterial catheter. We NIRS was used to determine quantitative changes in cerebral concentrations of oxygenated hemoglobin (DeltaHbO(2)) and deoxygenated hemoglobin (DeltaHHb), then calculated NIRS estimations DeltatHb (DeltaHbO(2)+DeltaHHb) and DeltaHbD (DeltaHbO(2)-DeltaHHb). Cerebral blood flow (CBF) was determined by colored microspheres, and mean artery blood pressure (MABP) measured by arterial catheter pressure transducer was recorded simultaneously. Linear regression methods were used to analyze the relationships between NIRS estimations, CBF measured by micropheres, and MABP.The correlation of NIRS estimations and CBF was quantitated by calculating coherence scores. A coherence of 1.0 indicates perfect correlation, a coherence of 0 indicates a complete lack of correlation. In the norm group, the experimental study showed strong correlations beween DeltaHbD, DeltatHb and changes in global CBF (GCBF), cerebral cortex CBF (CBFc), coherence scores r(1a) = 0.409, r(1b) = 0.440, r(2a) = 0.394 and r(2b) = 0.400, respectively, P0.05. In the hypotension group, the decrease of CBF was significant when the MABP dropped to 35 mm Hg (P0.05). With the decreasing MABP, there was a notable increase of DeltaHHb (P0.01), a modest increase (P0.05) at the beginning and then a marked fall (P0.01) of DeltaHbO(2) and DeltatHb was noted when the MABP dropped to 35 mm Hg. DeltaHbD decreased in parallel with the decline in CBF determined by colored microspheres, DeltaHbD varied with CBF during hypotensive episodes. Notably, there was a very strong correlations between DeltaHbD and changes in CBF (coherence scores GCBF r(3a) = 0.890, CBFc r(3b) = 0.887, P0.01); Importantly, decreases in DeltatHb did not correlate significantly with decreases in CBF during hypotension (coherence scores GCBF r(4a) = 0.395, CBFc r(4b) = 0.375, P0.05). Concordant changes (correlation coefficient0.5) in DeltaHbD, CBF and MABP, consistent with impaired cerebrovascular autoregulation, were observed in newborn piglets when MABP was less than 35 mm Hg. When MABP was more than 35 mm Hg, newborn piglets with intact cerebrovascular autoregulation in which CBF are maintained constant despite alternations in MABP have shown inconsistent changes in DeltaHbD, CBF and MABP (correlation coefficient0.5).DeltaHbD signal is more sensitive to changes in CBF than DeltatHb signal, in terms of cerebral hemodynamic changes both in normal and hypotensive conditions, while DeltatHb in normal condition. The lower limit of CBF autoregulation in newborn piglets aged 1 - 3 days was 35 mm Hg, and correlation between NIRS estimation (DeltaHbD) and MABP could be used to identify cerebrovascular autoregulation in newborn piglets.

To study the changes of the amplitude-integrated electroencephalography (aEEG) tracings within 6 hours after birth in term infants with hypoxic-ischemic encephalopathy (HIE) and explore the value of aEEG in early diagnosis and prediction of neurological outcome in term infants.From May 2003 to February 2005, 33 term infants with HIE at the Division of Neonatology, Pediatric Hospital of Fudan University were studied by aEEG within 6 hours after birth. The results of aEEG were categorized into three groups (normal, mildly abnormal and severely abnormal aEEG), while HIE was clinically classified into three grades (mild, moderate and severe) and the neurological outcomes at 18 months were assessed (normal, disabled and dead). The correlation between the results of aEEG, severity of HIE and neurological outcome at 18 months were analyzed, respectively. The values of aEEG on early diagnosis and neurological outcome prediction of HIE were analyzed.Among the 33 term infants with HIE, 20 infants had normal aEEG (normal amplitude aEEG), 5 had mildly abnormal aEEG (4 with mildly abnormal amplitude aEEG, 1 with normal amplitude and seizure) and 8 had severely abnormal aEEG (2 with mildly abnormal aEEG and seizures, 4 with severely abnormal amplitude and 2 with severely abnormal amplitude and seizures), respectively. Seventeen infants (51.5%) had mild HIE, 19 moderate (27.3%) and 7 (21.2%) severe HIE, respectively. Twenty-five cases were followed up, which showed that 19 had normal neurological outcome, 1 had disability and 5 died. By CMH square analysis and Spearman rank correlation analysis, the results of aEEG classification were correlated with the severity of HIE and the neurological outcome of term infants. Abnormal aEEG could predict the severity of HIE in term infants with a sensitivity of 100%, specificity of 81.3%, positive predictive value of 85.0% and negative predictive value of 100%, respectively. Abnormal aEEG could predict the neurological outcome of term infants with HIE, which showed a sensitivity of 100%, specificity of 90.9%, positive predictive value of 93.3% and negative predictive value of 100%, respectively. Severely abnormal aEEG could predict the severe HIE in term infants with sensitivity of 96.2%, specificity of 100%, positive predictive value of 100% and negative predictive value of 87.5%, respectively. Severely abnormal aEEG could predict the neurological outcome of term infants with HIE, which showed sensitivity of 94.7%, specificity of 100%, positive predictive value of 100% and negative predictive value of 85.7%, respectively.Monitoring with aEEG in term infants with HIE within 6 hours after birth could predict the severity of HIE and its neurological outcome at 18 months.

To investigate the protective effects of allopurinol (ALLO) on white matter damage in premature rats.An animal model for white matter damage was established by bilateral carotid artery occulation (BCAO). Eighty-four newborn SD rats (1 day old) were used in this study and were divided randomly into three groups [sham surgery (Sham); BCAO group (BCAO); allopurinol-treated group (ALLO)]. Pathological changes were studied 7 days and 14 days after BCAO, respectively. Myelin basic protein (MBP) was detected by immunohistochemistry 7 days and 14 days after BCAO, respectively. MBP-mRNA expression was determined 7 days and 14 days after BCAO respectively by reverse transcription-polymerase chain reaction (RT-PCR) with fluorescent quantitative method.In BCAO group, mild or severe rarefaction was found in 10 cases in the corpus callosum area, especially at the cingulum. Pathological changes of white matter were found in 4 cases in internal capsule. Subcortex white matter rarefaction was found in 8 cases. The extent of white matter rarefaction in ALLO group was reduced significantly. Enlargement of bilateral ventricles was found in 6 of 8 cases in BCAO group. The average ventricle size in ALLO group (2.44 +/- 0.71)% was reduced significantly as compared with that in BCAO group (3.27 +/- 0.73)% (P0.05). Strong MBP positive staining was found in sub-cortex, corpus callosum, hippocampus gyrus, and internal capsule of P14 sham surgery group. In BCAO group the MBP staining extent was reduced. The extent of MBP staining of ALLO group was between the other two groups. The optical density (OD) of MBP positive staining in BCAO group (6.60 +/- 0.68) was found higher than that in sham surgery group (9.40 +/- 0.53), the difference was statistically significant (P0.05). Compared with BCAO group, OD value in ALLO group (7.10 +/- 0.18) increased significantly (P0.05). RT-PCR data showed that MBP-mRNA copies (log10) in P7 and P14 rats of both BCAO and ALLO groups were lower than that in sham surgery group (P0.01); However, MBP-mRNA copies in ALLO group were higher than that in BCAO group (P0.05).BCAO could be used in newborn rats (1 day old) to establish a premature white matter damage (WMD) animal model. Allopurinol may have a potential protective effect on premature SD rat with ischemic WMD.

To study the change in regulation of cerebral blood flow (CBF) and cerebral metabolism rate (CMR) during selective head cooling (SHC) in newborn piglets.Sixteen newborn piglets, aged 5 approximately 7 days, were randomly assigned to one of the following three groups: SHC in normal piglets (n = 4), SHC after hypoxia-ischemia HI (n = 6) and normal temperature after HI (n = 6). Nasopharyngeal temperature was respectively reduced to 35 degrees C and then 32 degrees C in SHC group. HI was induced by using temporary occlusion of the bilateral carotid arteries and mechanical ventilation with low concentration of oxygen (6%) for 30 minutes. CBF was measured with color microspheres method. Mixed venous blood and arterial sample were collected at the same time from superior sagittal sinus and forelimb artery respectively for blood gas analysis, blood glucose and lactate measurement. Cerebral oxygenation metabolism rate (CMRO(2)), cerebral glucose metabolism rate (CMR(Glu)) and cerebral lactate production (CLP) were calculated.In normal piglets, CBF, CMRO(2) and CMR(Glu) were significantly decreased at 35 degrees C and 32 degrees C respectively, while CLP did not change. When nasopharyngeal temperature decreased to 35 degrees C, The ratios of CBF/CMRO(2), CBF/CMR(Glu) and CBF/CLP did not significantly change, coupling of CBF and CMR was maintained. While nasopharyngeal temperature decreased to 32 degrees C, the ratios of CBF/CMR(Glu) and CBF/CLP significantly decreased. Maintained newborn piglets normal temperature after HI, the CBF and CMRO(2) were significantly reduced, while CMR(Glu) and CLP were markedly increased. The ratio of CBF/CMRO(2) increased, CBF/CMR(Glu) and CBF/CLP decreased. Uncoupling of CBF and CMR was observed. During SHC after HI, the same decrease was observed in CBF and CMR(Glu) and CLP was markedly reduced. The ratio of CBF/CMRO(2), CBF/CMR(Glu) and CBF/CLP were restored at 35 degrees C and 32 degrees C as compared to the same time point in normal temperature, respectively.CBF and CMR decreased in normal piglets during SHC and coupling of CBF and CMR was maintained. After HI, CBF was reduced and the disturbance of cerebral oxygenation metabolism occurred. CBF and CMR was uncoupled. SHC after HI can improve CMR and correct uncoupling of CBF and CMR.

To investigate the protective effects of Huperzine A, a potent acetylcholinesterase inhibitor, against the hypoxic ischemic brain damage (HIBD) of the cognitive and morphology in the neonatal rats.Postnatal 7 days old rats were given vehicle or Huperzine A (0.05 mg/kg or 0.1 mg/kg, i.p.) following HIBD (unilateral carotid artery ligation followed by hypoxia) or sham operation, and then tested the learning ability and memory in the Morris water maze (MWM) from 36 to 40 postnatal days. The performance in MWM (escape latency, probe time) were recorded to evaluate the learning and memory dysfunction. At the end of MWM trials, the rats were decapitated and their brains were histologically analyzed. The tissue loss in different brain regions including striatum, cortex, and hippocampus were analyzed by image analysis system. The CA(1) subfield neurons numbers were counted to evaluate the brain damage. The acetylcholinesterase histochemistry staining was used to determine the activity of acetylcholinesterase in different brain regions.Compared with sham-operated group, HIBD rats with the vehicle treatment displayed significant tissue losses in the hippocampus (including CA(1) neurons), cortex, and striatum, as well as severe spatial memory deficits (escape latency: 44 s vs 30 s, P0.05, probe time: 14 s vs 40 s, P0.01). Huperzine A treatment (0.1 mg/kg) resulted in significant protection against both HI-induced brain tissue losses and spatial memory impairments (mean escape latency: 34 s vs 44 s, P0.05, probe time: 35 s vs 14 s,P0.01). However, Huperzine A treatment (0.05 mg/kg) did not show any significant improvement of spatial memory impairments (mean escape latency: 45 s vs 44 s, P0.05, probe time: 17 s vs 14 s, P0.05), but moderate to severe brain tissue losses. There was a pronounced reduction of CA(1) neuron density in ipsilateral hemisphere of vehicle-treated group and 0.05 mg/kg Huperzine A group compared with contralateral hemisphere or ipsilateral hemisphere of sham-operated group and 0.1 mg/kg Huperzine A group (72 vs 232, P0.01, 72 vs 229, P0.01, respectively). There was a close linear correlation between the CA(1) neurons cell number and the mean escape latency for 5 d acquisition trials (r = 0.777, P0.01).The unilateral HI brain injury in a neonatal rat model was associated with cognitive deficits, and that Huperzine A treatment may be protective against both brain injury and spatial memory impairment. Huperzine A showed a therapeutic potential for the treatment of hypoxic-ischemic encephalopathy (HIE) caused by the perinatal asphyxia.

To study the effects of hypothermia on cardiac function in neonates after birth asphyxia.Fifty term newborns with Apgar score5 at 5 minutes were randomly divided into no cooling group (normothermia group, NG; rectal temperature = 36.5 degrees C +/- 0.5 degrees C, n = 27) and cooling group (hypothermia group, HG; rectal temperature = 34.5 degrees C +/- 0.3 degrees C, nasopharyngeal temperature = 34.0 degrees C +/- 0.5 degrees C, n = 23). The selective head cooling was applied to maintain nasopharyngeal temperature at 34 degrees C for 72 h in hypothermia group. Systolic and diastolic function was detected at the end of treatment by echocardiogram.(1) The heart rate was obviously decreased during the hypothermia treatment, and there was a significant difference between HG and NG [(103 +/- 15) bpm vs. (126 +/- 14) bpm, P0.05]. No cardiac arrhythmia and hypotension were found in all neonates. (2) There were no significant differences on the ejection fraction, stroke volume and cardiac output of left ventricle between the two groups (P0.05). No significant difference was found in the numbers of left and right ventricular diastolic dysfunction, pulmonary hypertension between the two groups (P0.05). (3) The level of cardiac troponin T (cTnT) in plasma was (0.47 +/- 0.15) ng/ml in HG, and (0.35 +/- 0.21) ng/ml in NG, and there was no significant difference between the two groups (P0.05).No significant cardiac dysfunction complication caused by the hypothermia treatment was found in term neonates after birth asphyxia.

To establish a piglet model of acute hypoxic myocardial impairment.Nineteen newborn piglets were divided into two groups: control group (CON, n = 8) and asphyxia group (ASP, n = 11). In ASP group, asphyxia was induced by disconnecting the animal from the ventilator and clamping the inhalation tubing for 10 minutes. Six hours after cardiopulmonary resuscitation (CPR), the levels of serum creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) were detected. Cardiac functions were evaluated by echocardiography. Parameters included left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), ratio of peak E velocity and peak A velocity of mitral flow and tricuspid flow (MVE/A and TVE/A), ratio of peak velocity and a velocity of mitral annulus motion and tricuspid annulus motion (MVe/a and TVe/a), isovolumic relaxation time of left ventricle (LVIRT), index of mitral regurgitation and tricuspid regurgitation (MR and TR). The CON group was examined at the corresponding time points. The pathologic changes in piglets' hearts were examined. The myocardial histopathologic damage score (MHDS) was used to evaluate the severity of myocardial impairments.Six hours after CPR, the CK-MB and cTnT in ASP group [(423 +/- 156) IU/L and (0.85 +/- 0.64) microg/L] were both higher than those in CON group [(213 +/- 30) IU/L and (0.08 +/- 0.02) microg/L, P0.01]. The LVEF, RVEF, TVE/A, MVe/a and TVe/a in ASP group [(59.6 +/- 8.6)%, (60.2 +/- 7.1)%, 0.79 +/- 0.21, 0.77 +/- 0.12 and 0.78 +/- 0.19, respectively] were all lower than those in CON group [(67.5 +/- 6.9)%, (68.8 +/- 7.4)%, 1.14 +/- 0.16, 1.19 +/- 0.18 and 1.03 +/- 0.27, respectively, P0.05]. The MHDS in ASP group was higher (2.82 +/- 0.98) than that in CON group (0.38 +/- 0.53, P0.01), but no significant difference was observed in MHDS between the left ventricle and right ventricle.Asphyxia can lead to obvious myocardial impairment in newborn piglet, which could be very useful for the studies of acute hypoxic myocardial impairment in the newborn infants.

To evaluate dose response of inhaled nitric oxide (iNO) for surfactant-treated rabbits with meconium aspiration-induced acute lung injury (ALI) and hypoxemic respiratory failure (HRF), and variation of measured iNO by continuous NO delivery in pressure support ventilation (PSV).Adult rabbits (2.0 - 3.5 kg, n = 33) were randomized to receive intratracheal meconium instillation for 30 min and subjected to following treatment (n = 6 - 8). There were 4 groups: Control (C); NO, iNO at 1, 10, 20 and 40 x 10(-6) each for 60 min at 30 min interval of disconnection; Surf, intratracheal instillation of porcine lung surfactant phospholipids (100 mg/kg); SNO, both iNO and surfactant as in the NO and Surf groups; and a normal group (N), which did not undergo meconium aspiration but received sham deliveries of normal saline. All the animals were treated with PSV for 6 h. iNO levels at different input and sampling sites in the NO and SNO groups were detected by on-line chemiluminescent technique. The blood gas and lung mechanics were measured during the experiments every 2 h.(1) Meconium aspiration induced ALI and severe HRF (PaO(2)/FiO(2)200 mmHg) and depressed dynamic compliance of respiratory system (Cdyn) and airway resistance (Raw). In both Surf and NO groups modestly improved oxygenation was observed. In the SNO, values for PaO(2)/FiO(2) were improved from (185 +/- 39) mmHg at baseline to (301 +/- 123) mmHg at 6 h, while moderate or transient improvement was observed in both Surf and NO groups. Cdyn and Raw were only improved for short time in the Surf, NO and SNO groups. iNO had a mild response at 1 x 10(-6) to good response at 10 and 20 x 10(-6), but no further improvement occurred at 40 x 10(-6). The response of iNO in NO group was relatively transient compared to the SNO group. (2) When iNO was connected to the ventilator circuit, the connected site should be placed before humidifier to minimize fluctuation of iNO concentration, and sampling site for iNO monitoring should be placed adequately to eliminate artifact.iNO synergistically improved surfactant effects on oxygenation and lung mechanics. Continuous supply of iNO with non-continuous flow ventilator provided stable NO within accepted target range with least variation.