新生儿脑室内出血致脑积水的储液囊埋植引流治疗15例报告

目的 脑室内出血后脑积水是新生儿严重的并发症,存活后往往伴有严重的神经系统后遗症,目前对脑室内出血后脑积水处理仍然相当棘手,没有统一的方案.用储液囊埋植引流治疗新侣生儿脑室出血后脑积水,就其疗效和安全性作一初步评价.方法 对2003年1月至2005年12月期间,相继入住我院的15例新生儿脑窜内出血Ⅲ度以上合并脑积水,且1周内脑室进行性扩大,头围每天增大>2 mm伴有颅内压增高症状患儿,进行储液囊埋植引流治疗.储液囊埋植后根据临床和头颅超声或头颅CT检查结果,决定脑脊液引流次数,间歇引流时间和引流量,并观察脑脊液中细胞数、蛋白质和葡萄糖浓度的变化及术中和术后的并发症.若储液囊引流无效,改行脑室-腹腔分流术.出院后临床随访1.5～3年.结果 15例患儿中早产儿11例,孕龄(31.5±0.5)周;足月儿4例,其中3例为维生素K缺乏性颅内出血.脑室出血Ⅲ级13例,Ⅳ级2例.脑室出血平均诊断日龄:早产儿(9±1)d,足月儿(22±7)d.埋植Ommaya囊时日龄:早产儿(18±1)d,足月儿(31±7)d.平均每例患儿脑脊液引流次数(21.5±4.6)次,每次引流量为(10.2±1.3)ml/kg.15例经储液囊脑脊液引流后30 d脑脊液中细胞计数和葡萄糖分别为(14±6)×106个/L、(2.2±0.2)mmol/L;引流后39 d蛋白质为(0.48±0.10)g/L.13例经储液囊脑脊液引流后在1～4周内头围增长速度每周<1 cm,病情改善,其中12例至12～18个月时脑室恢复正常大小,1例在36个月时仍有轻度扩大.2例储液囊脑脊液引流无效,其中1例转行脑室.腹腔分流术后好转,1例放弃治疗出院后3个月死亡.术中和术后病情稳定,1例术后16 d储液囊出现渗漏,并发颅内感染(感染发生率为1/15),加用抗菌素治疗痊愈.14例术后1.5～3年时间随访:11例生长发育正常;2例早产儿发生两下肢痉挛性脑瘫,其中1例合并弱视;1例足月儿有癫癎发作.结论 采用储液囊脑室埋植引流治疗新生儿重型脑室出血合并脑积水,初步显示疗效满意和比较安全,为进一步明确其疗效需前瞻性临床多中心随机对照试验.     

Conservative treatment of non-resorptive hydrocephalus in premature infants

Following perinatal asphyxia and intracranial hemorrhage frequently progressive ventricular dilatation develops in preterm infants. Most common is communicating hydrocephalus due to obliterative arachnoiditis. Ventricular dilatation is reported to affect normal brain development and early therapy is recommended. Cerebrospinal fluid shunting is still accompanied by multiple complications, esp. in preterm infants with a birth-weight below 1,500 g. Seven preterm infants, born between the 27th and 34th gestational week with a birthweight of 910-1,940 g were medically treated for their progressive communicating hydrocephalus. The therapy consisted of intermittant lumbar punctures, medication of acetazolamide and furosemide as well as electrolyte and base replacement. Therapy was started at the 14th-31st postnatal day and lasted from 46 to 149 days. In all children the ventricular dilatation diminished. A steady state of cerebrospinal fluid production and absorption was regained in four children. Due to reoccurrence of ventricular dilatation shunting was performed in three others at the age of more than 3 months and with a weight of 3,620-5,170 g. Thus, medical therapy of hydrocephalus provides time for development of preterm infants, delay of shunting procedures and normalisation of cerebrospinal fluid dynamics.     

Posthemorrhagic hydrocephalus. Use of an intravenous-type catheter for cerebrospinal fluid drainage

STUDY OBJECTIVE: To report a 9-year experience with the treatment of posthemorrhagic hydrocephalus (PHH) with the use of an easily inserted external ventricular drain. DESIGN: A case series with a retrospective review of hospital records and cranial ultrasound results, from 1981 through 1989, in all infants with PHH. INTERVENTION: A previously defined method of identification and bedside management of PHH was applied. If infants reached 2 kg of body weight and PHH recurred, a ventriculoperitoneal shunt was inserted. RESULTS: A total of 70 procedures were performed in 24 patients, and all were associated with a decrease in head circumference and ventricular size on ultrasound scan. One infection occurred, and only 12 infants required a ventriculoperitoneal shunt. CONCLUSIONS: This technique compared favorably with other methods of intervention to avoid early placement of a ventriculoperitoneal shunt in preterm infants and offered the advantage of consistently decreasing ventricular size. A multicenter-controlled trial will be needed to compare the safety and efficacy of therapies for PHH.     

Changes in echogenicity of spinal subarachnoid space associated with intracranial hemorrhage: new observations

Purpose. The role of subarachnoid blood and secondary, sterile inflammation in the pathogenesis of posthemorrhagic hydrocephalus (PHH) is not well understood. The aims of this study were to study the frequency and rate of spread of blood into the spinal subarachnoid space (SSS) and to evaluate the relationship of this finding and PHH.¶Materials and methods. Nine premature babies with major intracerebral hemorrhage (ICH, grade 3 or higher), and ten premature infants with minor ICH (grade 1) or no evidence of ICH (control group) were identified and underwent serial cranial and spinal sonography at the time of initial diagnosis, 12–24 h after the ICH and weekly thereafter for at least 9 weeks. Sagittal and axial scans of the thoracolumbar spine were obtained and evaluated for the presence of echogenic debris in the dorsal SSS. Six additional patients who had cranial and spinal sonography died within the 1st week of life and underwent post-mortem examinations.¶Results. The SSS was echo-free (normal) in all cases at the time of initial sonographic diagnosis of ICH. Within 24 h, all babies with major ICH had developed increased echogenicity of the cervical and thoracic SSS. Echogenicity of the SSS decreased gradually over several weeks. Although transient ventricular dilatation was present in every patient, only one patient had rapidly progressive PHH requiring shunt placement. Transient cysts of the cervicothoracic subarachnoid space were identified in two patients 6–7 weeks after ICH. The subarachnoid space remained echo-free in all control infants At autopsy, all four infants with echogenic spinal debris had blood or blood products in the spinal subarachnoid space, whereas two infants with echo-free spinal images did not.¶Conclusions. Spread of blood from the ventricular system into the spinal subarachnoid space after ICH is common and can be seen within 24 h of initial ICH. Subarachnoid blood is associated with post-hemorrhagic ventricular dilatation and transient spinal subarachnoid cyst formation.     

Progressive posthämorrhagische Ventrikelerweiterung des Frühgeborenen Inzidenz, Prognose und Therapie

Background. 35% of preterm infants with intraventricular hemorrhage develop ventricular dilatation. The posthemorrhagic ventricular dilatation can persist, be transient or be progressive. Finally 1–2% of all very low birthweight (VLBW <1500 g) infants require shunt placement for the treatment of the posthemorrhagic hydrocephalus. Outcome. The neurodevelopmental outcome is extremely poor in children surviving progressive posthemorrhagic ventricular dilatation. Therapy. There are no uniform guidelines for the treatment of preterm infants with progressive posthemorrhagic ventricular dilatation. Randomised multicenter trials demonstrated, that inhibition of cerebrospinal fluid production with acetazolamide and furosemide or early cerebrospinal fluid tapping did not reduce the need for shunt placement and may worsen the outcome or can be associated with adverse side-effects. Preterm infants with posthemorrhagic ventricular dilatation should be treated by standard therapy with uniform guidelines for cerebrospinal fluid tapping and shunt placement.     

Prognosis and evolution of bilateral grade III intraventricular - hemorhages (III-III-IVH)

OBJECTIVE: To describe the evolution of bilateral III IVH so as to define optimal dates for therapeutic moves.METHODS: Longitudinal study of brain ultrasound scans from day 1 over the first three months of life. Our team calls "massive III" a hemorrhage with an intraventricular clot diameter >8mm on the coronal view at the level of Monro's foramina of the day of maximal hemorrhage. The 90 neonates were divided into four groups. Group I included 29 premature neonates who died in the first seven days after birth (birthweight (BW), 1,114 -/+253 g, gestational age (GA), 28 weeks 3 days); with 21 massive uni/bilateral grade III PIVH, and early filling of the whole ventricular system and cisterna magna. Group II included seven premature neonates who died in the second week after birth (similar in BW and GA, but more heterogeneous group). Two groups of infants survived for more than 14 days. Group III included 30 premature neonates (BW, 1,299 -/+260 g, GA, 29 weeks 1 day), with 20 classical grade III PIVH, who had post-hemorrhagic dilatation regressed spontaneously in 13 cases and regressed after acetazolamide treatment in 17 cases (five deaths due to three bronchopulmonary dysplasias and two periventricular leucomalacias). Group IV included 24 premature neonates (BW, 1,344 -/+289 g, GA, 29 weeks 5 days) with 15 massive grade III PIVH, who suffered posthemorrhagic hydrocephalus through obstruction of the Sylvius aqueduct (15) and/or of the cisterna magna (21), 12 blocks affecting both levels. Blocks were observed from day 8, and 35 in the quasi totality of cases (17 deaths).CONCLUSIONS: From 1,183 consecutive peri-intraventricular hemorrhages (PIVH) diagnosed by brain ultrasound studies (01/01/81-12/31/94), 90 were grade (III-III) PIVH, with a 36% overall survival. The massive volume of grade III PIVG plays a heavy role in early deaths of extremely low birthweight neonates and it heralds a blocked hydrocephalus in more vigorous infants who survive PIVH.     

Post-haemorrhagic hydrocephalus in the preterm infant

This prospective study documents the incidence, clinical features and risk factors for post-haemorrhagic hydrocephalus (PHH) as well as the short-term outcome after serial CSF taps. Serial real-time ultrasound scans were performed on 220 infants: on all admissions less than or equal to 1250 g and on an additional 130 infants with birthweights greater than 1250 g with risk factors for intraventricular haemorrhage (IVH). Based on percentile charts of postnatal increase in ventricular size and head circumference growth rate, PHH was defined as ventricular dilatation greater than 95th centile associated with either a head circumference growth greater than 95th centile or with clinical features of raised intracranial pressure (ICP). Forty-eight (22%) infants were found to have IVH of whom 14 had intracerebral extension of IVH. Sixteen (40%) of 40 infants who survived the acute episode of IVH developed PHH. PHH occurred more commonly in those who survived severe birth asphyxia and/or intracerebral extension of IVH. Fifteen infants who developed clinical features of raised ICP were treated with serial CSF taps. This procedure was effective in a staged treatment for PHH in relieving clinical symptoms and deferring ventriculo-peritoneal (VP) shunting. Morbidity associated with serial CSF taps and VP shunting is minimal. A high red cell count and protein concentration in the CSF at diagnosis of PHH identified all five infants who subsequently required VP shunting.     

Post-haemorrhagic hydrocephalus in the preterm infant

Abstract This prospective study documents the incidence, clinical features and risk factors for post-haemorrhagic hydrocephalus (PHH) as well as the short-term outcome after serial CSF taps. Serial real-time ultrasound scans were performed on 220 infants: on all admissions ≤1250 g and on an additional 130 infants with birthweights >1250 g with risk factors for intraventricular haemorrhage (IVH). Based on percentile charts of postnatal increase in ventricular size and head circumference growth rate, PHH was defined as ventricular dilatation >95th centile associated with either a head circumference growth >95th centile or with clinical features of raised intracranial pressure (ICP). Forty-eight (22%) infants were found to have IVH of whom 14 had intracerebral extension of IVH. Sixteen (40%) of 40 infants who survived the acute episode of IVH developed PHH. PHH occurred more commonly in those who survived severe birth asphyxia and/or intracerebral extension of IVH. Fifteen infants who developed clinical features of raised ICP were treated with serial CSF taps. This procedure was effective in a staged treatment for PHH in relieving clinical symptoms and deferring ventriculo-peritoneal (VP) shunting. Morbidity associated with serial CSF taps and VP shunting is minimal. A high red cell count and protein concentration in the CSF at diagnosis of PHH identified all five infants who subsequently required VP shunting.     

The assessment of perinatal brain damage in premature infants at risk by serial creatine kinase BB measurements]

Peri-intraventricular bleeding (PIVH) is considered the most common cause of neurologic damage or death in low birthweight infants (less than 1000 g birth weight and 31 weeks of gestation). High-resolution real-time ultrasound scan is used for early diagnosis of PIVH in neonates. Furthermore, increase of serum creatine-kinase BB (CK-BB) values has been found to be clinically useful for diagnosis and prognosis of several perinatal cerebrovascular injuries. Eighty-eight preterm infants with different grades of PIVH (I-IV) were studied by serial measurements of CK-BB levels in serum. No statistical correlation was found between enzymatic levels and severity of PIVH (p greater than 0.5).     

Erhöhte Konzentrationen des excitotoxischen Neurotransmiters Glutamat im Liquor von Frühgeborenen mit progressiver posthämorrhagischer Ventrikelerweiterung

Objective. Glutamate mediated excitotoxicity is responsible for neuronal injury in a variety of pathologic conditions. As cerebrospinal fluid (CSF) reflects the composition of the extracellular fluid of the brain, CSF-glutamate concentrations were determined in preterm infants with posthemorrhagic ventricular dilatation. Patients and Methods. 16 premature infants at the gestational age of 23–32 weeks who developed progressive posthemorrhagic ventricular dilatation were investigated during the first six months of life. CSF was obtained on 39 occasions by lumbar (n=4) or ventricular (n=23) puncture and during treatment with external drainage (n=12). Results. In 13 CSF samples from 7 patients (44% of the examined preterms) glutamate was increased (>7,2 μM). Extremely high CSF glutamate concentrations of 126 and 77 μM were observed in one patient during ventriculitis and during an episode with excessive increased intracranial pressure (67 cm H₂O). No correlation could be demonstrated between glutamate in the CSF and increased intracranial pressure or parenchym lesions. Elevated concentrations of glutamate in the CSF were associated with increased CSF lactate. Conclusion. These data demonstrate the occurrence of increased CSF glutamate up to the excitotoxic range in preterm infants with progressive posthemorrhagic ventricular dilatation. Glutamate may be part of the final pathway leading to neuronal injury in these patients.     

早产儿颅内出血振幅整合脑电图背景模式及睡眠觉醒周期的特点

目的 分析不同程度脑室周围-脑室内出血（PIVH）早产儿振幅整合脑电图（aEEG）背景模式及睡眠觉醒周期的特点。方法 选取56 例胎龄25~33 周的PIVH 早产儿及31 例同胎龄段无PIVH 早产儿,将PIVH 患儿按Papile 分级标准分为轻度出血组（Ⅰ、Ⅱ级）和中重度出血组（Ⅲ、Ⅳ级）,对各组早产儿aEEG的结果进行比较分析。结果 与轻度出血组及对照组比较,中重度出血组患儿的电压连续性降低,睡眠觉醒周期（SWC）缺失率高,aEEG 评分低（P 结论 aEEG 背景活动及SWC 的改变与早产儿PIVH 的严重程度有关。     

Soluble Fas (CD95/Apo-1), soluble Fas ligand,and activated caspase 3 in the cerebrospinal fluid of infants with posthemorrhagic and nonhemorrhagic hydrocephalus

Hydrocephalus may result in loss of tissue associated with neuronal degeneration, axonal damage, and reactive gliosis. The soluble form of the anti-apoptotic regulator Fas (sFas) and the pro-apoptotic factors soluble FasL (sFasL) and activated caspase 3 were studied in the cerebrospinal fluid of infants with hydrocephalus. Fifteen preterm infants with posthemorrhagic hydrocephalus undergoing serial reservoir puncture and seven term or near-term infants with nonhemorrhagic hydrocephalus and shunt surgery were included in the study. Twenty-four age-matched patients with lumbar puncture for the exclusion of meningitis served as controls. Elevated levels of sFas were observed in infants with posthemorrhagic hydrocephalus [median (range), 131 ng/mL (51-279 ng/mL)] and in nonhemorrhagic hydrocephalus [127 ng/mL (35-165 ng/mL)]. sFas concentrations were highest in a subgroup of eight patients with posthemorrhagic hydrocephalus developing periventricular leukomalacia [164 ng/mL (76-227 ng/mL)]. In contrast, in 24 control infants, sFas was low, in 15 cases below detection limit (0.5 ng/mL) and in nine cases, 24 ng/mL (20-43 ng/mL). sFasL and activated caspase 3 did not differ from control infants in all groups of patients. Increased intrathecal release of sFas in the cerebrospinal fluid of infants with hydrocephalus may serve as an indicator of brain injury from progressive ventricular dilatation.     

Posthaemorrhagic ventricular dilatation: new mechanisms and new treatment

Post haemorrhagic ventricular dilatation is associated with a high rate of disability, multiple impairments and adverse effects of shunt surgery for hydrocephalus. Post haemorrhagic ventricular dilatation results initially from multiple small blood clots throughout the cerebrospinal fluid channels impeding circulation and re-absorption. Transforming growth factor β is released into the cerebrospinal fluid and there is evidence that this cytokine stimulates the laying down of extracellular matrix proteins which produce permanent obstruction to the cerebrospinal fluid pathways. Prolonged raised pressure, pro-inflammatory cytokines and free radical damage from iron may contribute to periventricular white matter damage and subsequent disability. Interventions such as early lumbar punctures, diuretic drugs to reduce cerebrospinal fluid production and intraventricular fibrinolytic therapy have been tested and, not only fail to prevent shunt dependence, death or disability, but have significant adverse effects. Surgical interventions such as subcutaneous reservoir, external drain, choroid plexus coagulation and third ventriculostomy have not been subject to controlled trial. Ventriculoperitoneal shunt is not feasible in the early phase after intraventricular haemorrhage but, despite the problems with blockages and infections, remains the only option for infants with excessive head expansion over periods of weeks. We have piloted drainage, irrigation and fibrinolytic therapy as a way of removing blood early enough to stop the progressive deposition of matrix proteins, permanent hydrocephalus and shunt dependence.     

Posthaemorrhagic ventricular dilatation: new mechanisms and new treatment

Post haemorrhagic ventricular dilatation is associated with a high rate of disability, multiple impairments and adverse effects of shunt surgery for hydrocephalus. Post haemorrhagic ventricular dilatation results initially from multiple small blood clots throughout the cerebrospinal fluid channels impeding circulation and re-absorption. Transforming growth factor beta is released into the cerebrospinal fluid and there is evidence that this cytokine stimulates the laying down of extracellular matrix proteins which produce permanent obstruction to the cerebrospinal fluid pathways. Prolonged raised pressure, pro-inflammatory cytokines and free radical damage from iron may contribute to periventricular white matter damage and subsequent disability. Interventions such as early lumbar punctures, diuretic drugs to reduce cerebrospinal fluid production and intraventricular fibrinolytic therapy have been tested and, not only fail to prevent shunt dependence, death or disability, but have significant adverse effects. Surgical interventions such as subcutaneous reservoir, external drain, choroid plexus coagulation and third ventriculostomy have not been subject to controlled trial. Ventriculoperitoneal shunt is not feasible in the early phase after intraventricular haemorrhage but, despite the problems with blockages and infections, remains the only option for infants with excessive head expansion over periods of weeks. We have piloted drainage, irrigation and fibrinolytic therapy as a way of removing blood early enough to stop the progressive deposition of matrix proteins, permanent hydrocephalus and shunt dependence.     

A study of periventricular haemorrhage, post-haemorrhagic ventricular dilatation and periventricular leucomalacia in Chinese preterm infants

Serial cranial ultrasound scans were performed in 178 preterm Chinese infants (gestation less than 35 weeks, birthweight less than 2000 g) to study the incidence, age of onset and associating risk factors of periventricular haemorrhage (PVH), and also the occurrence of post-haemorrhagic ventricular dilatation and periventricular leucomalacia (PVL). Sixty-four infants developed haemorrhage, giving an incidence of 36%. Among infants of birthweight less than 1500 and less than 1000 g the respective incidence was 52 and 69%. Seventy-two per cent (46 of 64) of haemorrhages were initially detected within the first 3 days of life, but delayed haemorrhage occurring after 1 week of age occurred in nine infants. In eight of these infants PVH had been shortly preceded by a major clinical disaster. Eleven perinatal factors were found to be significantly associated with PVH but only systemic hypotension showed a significant independent association. Post-haemorrhagic ventricular dilatation developed in 17 (46%) of the 37 infants who survived for more than 1 month after PVH. This was transient in 41%, persistent but stable in 29% and progressive in 29%. PVL was detected in eight infants who survived the initial period following PVH.     

Phase I study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus.

AIM: Phase I study to evaluate intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) as a method of clearing blood from the cerebrospinal fluid, and thus preventing permanent hydrocephalus. METHODS: Twenty two preterm infants, aged 7 to 26 days, with progressive posthaemorrhagic ventricular dilatation (ventricular width > 4 mm over 97th centile) received one to five intraventricular bolus injections of 1.0 mg or 0.5 mg tPA at intervals of one to seven days. RESULTS: The mean cerebrospinal fluid concentration of tPA 24 hours after 1 mg was 1860 micrograms/ml. The half life of tPA in cerebrospinal fluid was about 24 hours. Twenty one (95%) infants survived, 12 (55%) without shunt surgery. One infant had secondary intraventricular haemorrhage. CONCLUSION: Intraventricular tPA resulted in survival without a shunt for most of the infants, but with some risk. Failure may have been due to plasminogen deficiency, an inhibitor, or late intervention.     

Diagnosis and clinical course of cerebral hemorrhage in infants based on sonography

Infants of very low birth weights (less than 1500 g) born before the 32nd week of gestation have a high incidence of neonatal intracranial hemorrhage (ICH). Beside perinatal and postnatal asphyxia the main risk factor for ICH is the immaturity of the infant. Mild intracranial hemorrhages resolve within a few weeks. Severe ICH, which were seen in very immature babies before 30 weeks of gestation and with birth-weights below 1250 g had a fatal outcome. The mortality rate in severe ICH was 50%. The infants which survived severe ICH developed posthemorrhagic hydrocephalus (PHH). Using the open fontanelle as an acoustic window gray scale ultrasonography of children's brain is able to visualize ICH and PHH. We suggest early sonografic brain investigation within the first days of life in all prematurely born infants with perinatal asphyxia. Infants with severe ICH should have weekly sonografic controls, to detect PHH as soon as possible.     

Background patterns and sleep-wake cycles on amplitude-integrated electroencephalography in preterms younger than 30 weeks gestational age with peri-/intraventricular haemorrhage

AIM: The objective of this prospective study was to evaluate the influence of peri-/intraventricular haemorrhage (PIVH) grades I-IV on amplitude-integrated electroencephalographic (aEEG) activity in preterm infants<30 weeks gestational age (GA). METHODS: The aEEG tracings of the first 2 weeks of life of 56 preterm infants younger than 30 weeks GA (2 groups: group A=23-26 weeks GA, group B=27-29 weeks GA) born during a 4-year period with PIVH grades I-IV were assessed for the relative duration of four background aEEG activity patterns (continuous pattern, discontinuous high-voltage pattern, discontinuous low-voltage pattern and nearly isoelectric pattern), the presence of seizure activity and the appearance of sleep-wake cycles and compared to the tracings of 75 neurologically healthy preterms without PIVH. RESULTS: Analysis of aEEG background activity showed a decrease of continuous activity whereas discontinuous activity increased in both groups with larger haemorrhages (grades III and IV) and when compared to controls. Suspected seizure activity was more common with increasing degree of bleeding in group A (50% with PIVH I or II, 75% with PIVH III or IV) and when compared to controls and was the same with increasing degree of bleeding in group B (47% with PIVH I or II, 45% with PIVH III or IV). Sleep-wake cycles were less common with larger haemorrhages in both groups (group A: 41% with PIVH I or II, 25% with PIVH III or IV; group B: 52% with PIVH I or II, 9% with PIVH III or IV) and when compared to controls. CONCLUSIONS: The aEEG characteristics of severe PIVH consist in a combination of a more discontinuous background pattern, a lack of sleep-wake cycles and a higher likelihood of seizure activity when compared to age-matched controls.     

Plasma guanosine 3',5'-cyclic monophosphate and severity of peri/intraventricular haemorrhage in the preterm newborn

A poorly controlled cerebral circulation, caused by excessive production of nitric oxide, has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, cGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome. Conclusion: Increased cGMP levels are associated with the development of PIVH. It is suggested that vasodilatory nitric oxide-induced impairment of cerebral autoregulation plays a role here.     

早产儿脐血维生素K依赖因子水平及产前补充维生素K1对其影响的研究

目的了解早产儿是否存在维生素(Vit)K依赖因子水平低下及其与早产儿脑室周围-脑室内出血的关系,探讨产前补充维生素(Vit)K1对早产儿血浆VitK依赖因子水平的影响及对脑室周围-脑室内出血的预防作用.方法将有早产可能且至分娩时孕周不足35周的孕妇分为两组对照组133例,在产前给予地塞米松注射;对照组44例,产前给予地塞米松+VitK1.两组早产儿各30例留取脐动脉血离心零下20℃以下保存用凝固法检测Ⅱ、Ⅶ、Ⅸ、Ⅹ等凝血因子活性水平,同时留取同期出生的健康足月新生儿30例脐血标本作对照.两组早产儿生后1周内常规作头颅超声检查以明确有无脑室周围-脑室内出血及其程度.结果早产儿与足月新生儿脐血VitK依赖因子活性水平分别为Ⅱ(25.6±9.5)%对(36.7±4.9)%,Ⅶ(59.0±17.7)%对(64.5±10.6)%,Ⅸ(24.7±8.9)%对(30.2±5.7)%,Ⅹ(30.2±5.0)%对(34.3±12.6)(P<0.05).母亲产前补充VitK1后其婴儿脐血VitK依赖因子水平分别为Ⅱ(36.4±6.9)%,Ⅶ(69.6±16.6)%,Ⅸ(25.7±10.9)%和Ⅹ(39.3±8.0)%,除Ⅸ因子外,Ⅱ、Ⅶ和Ⅹ因子活性均显著升高(P<0.05).脑室周围-脑室内出血发生率在对照组为52.6%,观察组为31.8%(χ2=5.744,P=0.017);重度出血对照组为12.0%,观察组为2.3%(χ2=3.626,P=0.057).结论早产儿存在VitK依赖因子水平低下,可能为其易于发生脑室周围-脑室内出血的原因之一.分娩前母亲补充VitK1可显著提高其血浆Ⅱ、Ⅶ和Ⅹ因子水平,并对脑室周围-脑室内出血有一定的预防作用.