Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants

BACKGROUND: Despite rapid advances in the management of preterm infants, periventricular leukomalacia (PVL) remains a considerable problem in neonatal intensive care. The aim of this study was to determine whether hypocarbia is associated with the development of PVL in mechanically ventilated, preterm infants and to emphasize the importance of avoiding this disturbance. METHODS: The authors evaluated 52 mechanically ventilated infants with a gestational age of <34 weeks, who exhibited hypocarbia in the first three postnatal days (lowest carbon dioxide tension being <25 mmHg). These infants were then compared with 52 infants in a control group not exhibiting hypocarbia, matched for birthweight and gestational age. A diagnosis of PVL was made on the basis of the results of cranial ultrasonography. Confounding factors potentially associated with the development of PVL were controlled in logistic regression analyses. RESULTS: Of the 52 mechanically ventilated preterm infants with hypocarbia, 10 (19.2%) developed cystic PVL, and six (11.5%) developed periventricular echodensity. Of the 52 infants in the control group only two (3.8%) developed cystic PVL, and one (1.9%) infant developed periventricular echodensity. The authors observed no significant differences in other prenatal and perinatal risk factors between the two groups. CONCLUSION: Hypocarbia in mechanically ventilated preterm infants during the first days of life is suggested as being an independent predictor of PVL, predisposing these infants to subsequent neurodevelopmental delay.     

Cerebral palsy of cystic periventricular leukomalacia in low-birth-weight infants

We studied ultrasound findings and neurodevelopmental outcome of 24 infants weighing 2500 g or less with cystic periventricular leukomalacia. Fourteen infants had symmetrical cysts in the parietal or occipital region (group 1) and 10 had non-symmetrical cysts (group 2). Each infant was followed for more than 4 years of age (mean 5 years and 7 months). Twenty out of 24 (83.3%) children developed cerebral palsy. All of group 1 had cerebral palsy (8 diplegia and 6 ataxic diplegia), while 6 (60%) in group 2 developed cerebral palsy (4 diplegia and 2 hemiplegia). There was a significant difference in the incidence of cerebral palsy and motor ability between the two groups. The size and site of the cyst did not predict cerebral palsy. The presence of symmetrical cysts in the parietal or occipital region is a highly reliablable neurosonographic finding for predicting cerebral palsy.     

Early hypocarbia of preterm infants: its relationship to periventricular leukomalacia and cerebral palsy, and its perinatal risk factors

AIM: To clarify clinical interactions between early hypocarbia, periventricular leukomalacia (PVL) and cerebral palsy of preterm infants. METHODS: Serial measurements of PaCO2 using arterial blood samples at 3, 6, 12, 24 and 48 h of life were performed for 115 very-low-birthweight infants admitted between 1995 and 1999. Severe early hypocarbia, defined when at least two of five PaCO2 values showed 3.3 kPa or less, was observed in eight infants (hypocarbia group). Preterm PVL was diagnosed by serial ultrasonographic examinations and cranial magnetic resonance imaging, and subsequently classified into early-onset PVL diagnosed within 14 d, or late-onset PVL after 14 d. Perinatal risk factors for early hypocarbia were investigated from the mothers' records and interviews with obstetricians. RESULTS: The average birthweight in the hypocarbia group was significantly smaller than that in the control group (p < 0.01). The occurrence of PVL in the hypocarbia group was not different from that in the control group. Early hypocarbia was significantly related to late-onset PVL (p < 0.001), but not related to early-onset PVL. The incidence of cerebral palsy in the hypocarbia group was significantly higher than that in the control group (p < 0.001). Multivariate analysis showed that both low birthweight and number of maternal previous abortions were predictive for early hypocarbia. CONCLUSION: Early hypocarbia of preterm infants in our hospital was significantly associated with both cerebral palsy and late-onset PVL, but not with early-onset PVL. The background of the three clinical events, early hypocarbia, PVL, and cerebral palsy, may not be identical in human newborns.     

Neonatal MRI in preterm infants with periventricular leukomalacia and mild disability

Background: The aim of the present study was to describe the neonatal magnetic resonance imaging (MRI) findings of preterm infants with periventricular leukomalacia and mild neurological disability. Methods: MRI findings at term equivalent were retrospectively investigated in eight preterm infants with mild disability and periventricular leukomalacia diagnosed on MRI in infancy. Results: Linear, spotted, or macular areas of hyperintensity on T1‐weighted imaging and hypointensity on T2‐weighted imaging were identified in all subjects in the white matter lateral to the body of the lateral ventricle. No cystic lesions were seen. These findings were more widespread and more clearly visualized on T2‐weighted imaging than T1‐weighted imaging. Conclusions: Linear, spotted, or macular lesions that are hyperintense on T1‐weighted imaging and hypointense on T2‐weighted imaging are possibly compatible with periventricular leukomalacia.     

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目的探讨早产儿囊性脑室周围白质软化症(cPVL)与低碳酸血症及机械通气的关系。方法比较cPVL与非cPVL早产儿(各10例)生后3d内发生的低碳酸血症(至少2次PaCO2<3.33kPa)情况以及每天机械通气参数,两组在胎龄、出生体重、性别及临床情况方面统计均无差异。结果cPVL组发生低碳酸血症几率为70%,明显高于非cPVL组的20%(P=0.02),而两组每天机械通气参数无差异。结论早产儿cPVL的发生与低碳酸血症有关,似乎与过度通气无关。     

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??Abstract:Objective??Using the skill of head ultrasound to make an early diagnosis for preterm infants with periventricular leukomalacia??PVL????analyze some related risk factors which may result in PVL. Methods??Between Jan. 2006 and Jun. 2009??443 preterm infants were chosen?? who were born in Anhui Provincial Children’s Hospital. All subjects were divided into PVL group??125?? and non PVL group??318????non Cystic PVL group??116?? and Cystic PVL group??9?? by different grades of PVL. The factors of PVL were analyzed by Backward Stepwise Logistic regression. Results??Univariate factor analysis showed?? the difference was significant ??P < 0.05 or P < 0.01??among gestational age?? birth weight?? delivery pattern?? hypothermia?? apnea?? blood sugar?? myocardial enzyme?? postnatal infection?? cAMP receptor protein and albumin between PVL group and non PVL group. Multiple factors Logistic regression showed?? low birth weight and incidence of uterine-incision delivery?? postnatal infection?? higher level of myocardial enzyme and albumin were risk factors of PVL?? and postnatal infection was risk factor of cystic PVL. Conclusion??Low birth weight?? spontaneous delivery?? postnatal infection and high levels of albumin and myocardial enzyme are risk factors of PVL. Preterm infants with postnatal infection have higher incidence of cystic PVL.     

白介素18与早产儿脑室周围白质软化的相关性研究

目的 探讨白介素18(IL-18)在早产儿脑室周围白质软化(PVL)发病机制中的作用,为早产儿PVL的早期诊断及防治提供可能的理论依据.方法 经头颅B超诊断为PVL早产儿21例,对照组早产儿20例,应用酶联免疫吸附试验测定出生6 h内血清IL-18值.结果 根据头颅B超结果,将PVL组患儿分为Ⅰ级8例,Ⅱ级6例,Ⅲ级5例及Ⅳ级2例.Ⅰ级PVL患儿血清IL-18水平明显高于对照组(P<0.05);Ⅱ级PVL患儿明显高于Ⅰ级(P<0.05);Ⅲ级明显高于Ⅱ级(P<0.05).PVL组脑瘫发生率明显高于对照组(P<0.05).结论 早产儿血清IL-18水平升高与早产儿PVL的发生密切相关,在出生时可作为一个早期预测指标,并为防治早产儿PVL发生提供可能的理论依据.     

早产儿囊性脑室周围白质软化症高危因素探讨

目的探讨早产儿囊性脑室周围白质软化症(cPVL)的高危因素。方法对cPVL(12例)与非cPVL早产儿(30例)进行回顾性研究,对多种围产期高危因素进行Logistic回归分析。结果胎膜早破、生后48 h内PaCO2<3.33 kPa(25 mm Hg)、生后4 h内pH<7.25、生后1周内发现脑室周围强回声的OR值分别为2.125、3.312、2.820和3.712(P<0.05或P<0.01)。结论胎膜早破、生后48 h内PaCO2<3.33 kPa、生后4 h内pH<7.25、生后1周内脑室周围有强回声为早产儿cPVL的高危因素。     

Thalamic lesions revealed by MR associated with periventricular leukomalacia and clinical profiles of subjects

Magnetic resonance (MR) findings at the cerebral white matter and the thalamus in 44 children with spastic cerebral palsy born at preterm were analysed. Periventricular leukomalacia (PVL) was found in all of the children. Lesions of the thalamus were revealed in 22 children, 19 of which were in the anterior part of the pulvinar and 3 of which were in other areas. Gestational ages and birthweights of the children with a lesion of the pulvinar were significantly greater than those without lesions of the thalamus. Mental retardation and paroxysmal ocular downward deviation were more frequently seen in the children with a lesion of the pulvinar than in those without lesions of the thalamus. The children with thalamic lesions in areas other than the pulvinar showed the most severe motor and mental disabilities.     

National survey of periventricular leukomalacia in Japan

Abstract Background: Clarification of the present status of periventricular leukomalacia (PVL) in Japan.
Methods: Questionnaires were mailed to the leading neonatal intensive care units (NICU) and rehabilitation centers for children.
Results: The incidence of PVL in the group of surviving preterm infants of gestational ages less than 33 weeks was 4.8–4.9% on ultrasound and 7.7–7.9% on magnetic resonance imaging and/or computed tomography. The incidence of PVL did not decrease between 1990 and 1994. The incidence of PVL in the NICU varied from 0 to 47.1%. Infants from multiple pregnancies had a higher incidence (9.1%) of PVL than those from single pregnancies (6.2%). The proportion of PVL in all patients in rehabilitation centers with cerebral palsy (CP) has increased recently.
Conclusions: It was roughly calculated that about 750 cases of CP with PVL occurred annually in Japan, thus accounting for about one-third of the total number of cases of CP.     

Risk factors for cerebral palsy in preterm infants

OBJECTIVE: To identify crucial factors that precipitate cerebral palsy by controlling confounding factors in logistic regression analyses. DESIGN AND PATIENTS: We retrospectively investigated a cohort of all 922 infants with gestational ages of less than 34 weeks (22-33 weeks), who were admitted to our neonatal intensive care unit between 1990 and 1998. Thirty (3.7%) were diagnosed to have cerebral palsy. We analyzed the prenatal and postnatal clinical variables of the cerebral palsy cases and compared them with 150 randomly selected controls. RESULTS: Risk factors for cerebral palsy identified in univariate analysis were: twin pregnancy, long-term ritodrine tocolysis, respiratory distress syndrome, air leak, surfactant administration, intermittent mandatory ventilation, high frequency oscillation, lowest PaCO2 levels, prolonged hypocarbia during the first 72 h of life, and postnatal steroid therapy. In a conditional multiple logistic model, long-term ritodrine tocolysis, prolonged hypocarbia and postnatal steroid therapy remained associated with an increased risk of cerebral palsy after adjustment for other antenatal and postnatal variables (OR [Odds Ratio] = 8.62, 95% CI [Confidence Interval], 2.18-33.97; OR = 7.81, 95% CI, 1.42-42.92; OR = 21.37, 95% CI, 2.01-227.29, respectively). CONCLUSIONS: Our results suggest that long-term ritodrine tocolysis underlines the development of cerebral palsy. Further assessments of the effect of ritodrine on fetal circulation and nervous system are required. Moreover, possible alternatives to systemic postnatal steroids are needed, and carbon dioxide levels should be more strictly controlled.     

神经节苷脂和脑活素治疗早产儿脑室周围白质软化的疗效观察

目的探讨应用神经节苷脂(GM-1)和脑活素治疗早产儿脑室周围白质软化的临床疗效。方法将86例确诊为脑室周围白质软化的患儿随机分为三组。Ⅰ组(对照组)27例,采用保暖、吸氧、控制感染、纠正酸碱及电解质紊乱、维持正常血糖、血压、血气等常规治疗;Ⅱ组31例,在常规治疗基础上加用脑活素静脉注射;Ⅲ组28例,在常规治疗基础上加用GM-1静脉注射。定期观察和随诊颅脑B超的变化,进行统计学分析。结果GM-1治疗组治疗有效率优于对照组,差异有统计学意义(P<0.05);脑活素治疗组治疗有效率高于对照组,但差异无统计学意义。结论神经节苷脂是治疗早产儿脑室周围白质软化的有效药物之一,脑活素治疗早产儿脑室周围白质软化的有效性尚待进一步研究。     

Timing and antecedents of periventricular haemorrhage and of cerebral atrophy in very preterm infants

The brains of 95 consecutively admitted infants born at less than 33 weeks gestation were scanned with ultrasound. Thirty-six (38%) had periventricular haemorrhage (PVH). Eight (8%) had cerebral atrophy (together with PVH in 5).Twelve (40%) of the 30 infants in whom satisfactory timing of PVH was possible bled on the first day of life, but the median age when PVH was first detected was during the second day. The median age when PVH reached its maximum extent was the fourth day. The most significant antecedents of PVH were very short gestation and the presence of severe respiratory illness, particularly hyaline membrane disease, necessitating mechanical ventilation. Analysis of variance showed that pneumothorax arising during ventilation was the single most significant antecedent of PVH. Other significant antecedents, notably prolonged coagulation times, were found almost exclusively in infants with severe respiratory illness.Cerebral atrophy appeared usually to be attributable either to severe asphyxia during delivery or later, or to the formation of cysts at the site of previous haemorrhage into brain tissue.     

Episodes of hypocarbia and early-onset sepsis are risk factors for cystic periventricular leukomalacia in the preterm infant

Background

Septic episodes in preterm infants recently have been reported to be associated with periventricular leukomalacia (PVL). The role of hypocarbia as an independent risk factor for PVL in clinical studies raises many questions without conclusive answers.

Aims

To evaluate risk factors for cystic PVL focussing on the influence of hypocarbia.

Study design

Retrospective single centre case-control study.

Subjects

Preterm infants 24 to 35 weeks of gestational age and matched (1:2 for gender, birth year, gestational age and birth weight) controls.

Outcome measures

Multivariate analysis of perinatal factors being associated with cystic PVL diagnosed by serial ultrasound examinations.

Results

Univariate analysis of risk factors revealed lower 5 and 10 min Apgar scores, and higher rates of neonatal seizures, early-onset sepsis, neonatal steroids, respiratory distress syndrome with surfactant replacement therapy, and episodes of hypocarbia significantly being associated with PVL. Multivariate analysis using a logistic regression model revealed early-onset sepsis and hypocarbia being significantly associated with PVL (p = .022 and .024, respectively). Lowest PaCO₂ values did not differ as did not the duration of hypocarbia, but the onset of hypocarbia was significantly later in PVL cases compared to controls (mean 26 vs. 15 h, p = .033). Neurodevelopmental follow-up at a median time of 46 months was poor showing 88% of the cases having an adverse neurological outcome.

Conclusion

We found early-onset sepsis and episodes of hypocarbia within the first days of life being independently associated with PVL.     

磁敏感加权成像在早产儿伴脑室旁白质损伤中的应用研究

目的脑室旁白质损伤是早产儿围生期窒息后常见的脑损伤类型之一,其MRI表现具有特征性,但常规序列难以区分病灶内是否合并出血,而出血与否可能影响治疗和预后。该研究应用磁敏感加权成像(SWAN)来检测存在白质损伤的早产儿脑内的出血性病变。方法对临床怀疑围生期窒息后脑损伤的75例早产儿行头颅GE HDx Twin Speed 3.0T MRI检查,扫描序列包括T1FLAIR、T2FLAIR、DWI和SWAN。结果44例(58.7%)早产儿存在脑室旁白质损伤,其中4例(9.1%)存在出血性白质损伤。在这4例中有3例合并生发基质出血-脑室内出血;4例合并小脑出血;1例合并蛛网膜下隙出血。结论脑室旁白质损伤中绝大多数为非出血性损伤,当伴有生发基质出血或脑室内出血时,脑室周围白质损伤病灶中常存在出血。     

Late-onset circulatory dysfunction of premature infants and late-onset periventricular leukomalacia

Background: The sudden appearance of hypotension and oliguria without obvious cause following stable circulation and respiration in preterm infants is frequent in Japan. Such episodes are referred to as late‐onset circulatory dysfunction of premature infants (LCD). Volume expanders and inotropic agents are often ineffective against this condition, whereas i.v. steroids are significantly effective. A major problem is that cystic periventricular leukomalacia (PVL) often develops a few weeks after an episode. The aim of the present study was to clarify the risk factors, including LCD, related to cystic PVL. Methods: A case–control study was performed for preterm infants who were delivered at <33 weeks of gestation and admitted to seven neonatal intensive care units in Japan. Cystic PVL infants were stratified into early‐onset PVL diagnosed within 28 days of age and late‐onset PVL diagnosed after more than 28 days of age. The reported and new risk factors for PVL, for each group of PVL infants, and for all PVL infants, were compared with controls. Results: Thirty‐two infants were diagnosed with cystic PVL (17 early‐onset and 15 late‐onset). All PVL infants significantly differed from controls on Apgar score, number of abortions and pregnancies, intraventricular hemorrhage, and LCD. LCD was diagnosed in 28.1% of both PVL groups compared with 6.3% of controls (P = 0.02). Multivariate analysis demonstrated significant association between late‐onset PVL and LCD. Conclusion: LCD was significantly associated with cystic PVL, especially late‐onset PVL. Elucidating the cause of LCD might reduce the incidence of PVL and improve the neurological prognosis of preterm infants.     

中国人群早产儿脑室周围白质软化危险因素的meta分析

目的探讨中国人群早产儿发生脑室周围白质软化的主要危险因素,为今后防治工作提供依据。方法利用meta分析方法分析国内14篇关于早产儿脑室周围白质软化危险因素的研究文献。累计病例748例,对照3 366例。根据齐性检验结果选择计算各危险因素合并比值比(OR)及其95%可信区间(95%CI)模型。结果脑室周围白质软化发生的OR值(95%CI)分别为:产前使用激素0.46(0.34～0.61),胎膜早破3.60(1.40～9.24),胎龄5.05(2.66～9.58),低出生体质量2.78(2.30～3.35),重度窒息5.35(2.09～13.68),感染4.46(3.08～6.44),机械通气3.67(1.74～7.72),低碳酸血症4.49(2.03～9.94),脑室内出血2.00(1.15～3.45),酸中毒1.58(1.19～2.08)。结论胎膜早破、胎龄、低出生体质量、重度窒息、感染、机械通气、低碳酸血症、脑室内出血和酸中毒是中国人群早产儿脑室周围白质软化发病的主要危险因素,产前使用激素可能为脑室周围白质软化的保护因素。