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.     

Etiological factors associated with the development of periventricular leukomalacia

Prenatal, intrapartum and postnatal factors are compared between 15 preterm infants, known to have periventricular leukomalacia (PVL) on ultrasound and 15 infants of similar birthweight and gestation who ultrasonographically showed no evidence of cystic lesions, and who are known to be neurologically normal at follow up. Prenatally, the incidence of antepartum haemorrhage was significantly higher in the PVL group. Intrapartum factors were similar between the two groups but postnatally, the PVL group had significantly lower PaCO2 readings during the first 72 h of life. It is postulated that a severe maternal bleed in late pregnancy and neonatal hypocarbia could significantly decrease cerebral perfusion and cause areas of ischaemia and infarction resulting in periventricular leukomalacia.     

Etiological Factors Associated with the Development of Periventricular Leukomalacia

ABSTRACT. Prenatal, intrapartum and postnatal factors are compared between 15 preterm infants, known to have periventricular leukomalacia (PVL) on ultrasound and 15 infants of similar birthweight and gestation who ultrasonographically showed no evidence of cystic lesions, and who are known to be neurologically normal at follow up. Prenatally, the incidence of antepartum haemorrhage was significantly higher in the PVL group. Intrapartum factors were similar between the two groups but postnatally, the PVL group had significantly lower PaCO₂ readings during the first 72 h of life. It is postulated that a severe maternal bleed in late pregnancy and neonatal hypocarbia could significantly decrease cerebral perfusion and cause areas of ischaemia and infarction resulting in periventricular leukomalacia.     

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.     

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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。     

Neonatal neurosonographic correlates of cerebral palsy in preterm infants

Serial neurosonographic examinations are routinely performed at frequent intervals during the nursery course of all preterm infants of 33 weeks or less gestation who are admitted to the intensive care nursery of Thomas Jefferson University Hospital. After discharge, the following survivors during the past 5 years had repeated ultrasound examinations until the anterior fontanel closed and clinical assessments until the presence or absence of cerebral palsy at a minimum age of 12 months was established: all infants with grade III/IV intracranial hemorrhage, periventricular echodensity and periventricular cyst formation, selected infants with either normal ultrasound findings or grade I/II intracranial hemorrhage. Fifteen survivors were found to have cerebral palsy, and all had at least one of the following ultrasound abnormalities: diffuse, bilateral, and multiple periventricular cysts 3 mm or more in diameter that persisted beyond term age, bilateral asymmetrical dilation of the lateral ventricles following grade III intracranial hemorrhage with small periventricular cysts, and ventricular porencephaly following an ipsilateral grade IV intracranial hemorrhage. The periventricular cysts were usually preceded by extensive echodensities of the white matter surrounding the lateral ventricles; these findings were suggestive of periventricular leukomalacia and were the most common abnormal findings on ultrasound in the infants with cerebral palsy. Of 124 infants without cerebral palsy, 121 had no or less severe abnormal findings on ultrasound; the exceptions were three infants with bilateral persistent large periventricular cysts who had normal motor development in late infancy.     

Early detection of delayed myelination in preterm infants

Myelination of the central nervous system can be demonstrated with magnetic resonance imaging. The influence of periventricular-intraventricular hemorrhage and periventricular leukomalacia on cerebral myelination was studied using magnetic resonance imaging. The subjects were 33 preterm infants of less than 30 weeks' gestation studied at 44 weeks' postmenstrual age: 11 infants with periventricular-intraventricular hemorrhage, 7 with periventricular leukomalacia, and 15 without periventricular-intraventricular hemorrhage or periventricular leukomalacia. There were no differences in mean gestational age and birth weight between the three groups. However, infants without periventricular-intraventricular hemorrhage or periventricular leukomalacia had significantly less respiratory distress syndrome. At 44 weeks postmenstrual age, infants with periventricular leukomalacia had a significantly delayed myelination pattern (stage M2) in comparison with infants without periventricular-intraventricular hemorrhage or periventricular leukomalacia and infants with periventricular-intraventricular hemorrhage (stages M3 and M4). The latter two groups had myelination stages that were similar to those of healthy term infants at 44 weeks' postmenstrual age. The results demonstrate that periventricular leukomalacia causes delayed myelination of the cerebrum, whereas periventricular-intraventricular hemorrhage does not.     

Respiratory distress syndrome, early postnatal corticoid therapy and periventricular leukomalacia]

The aetiology of cavitating periventricular leukomalacia (cPVL) involves pre and perinatal factors. Early postnatal dexamethasone has been associated with an increase in cerebral palsy but its role in the development of PVL remains uncertain. OBJECTIVES: (1) Reevaluate major factors associated with cPVL, (2) Evaluate the potential effect of early postnatal dexamethasone. METHOD: This retrospective case-control study (matched for gestational age, birth weight, twin pregnancy and date of birth) compared 50 premature infants with cPVL diagnosed between D7 and D45 from 1995 to 2000 and 50 matched control newborns with normal serial neurosonograms. A data base with 97 selected perinatal variables was used to perform logistic regression analysis in controlling confounding variables, the results are expressed as adjusted Odds Ratio (OR) with 95% confidence interval. RESULTS: The two populations were comparable for gestational age (median: 29.3 weeks, range: 24.4-34.7) and birth-weight (1297 g, 645-2130 g). The annual incidence of cPVL in preterm infants with a gestational age < 33 weeks varied from 1995 to 2000: 1.3%, 4.5%, 13.4%, 2.1%, 3%, 2.9%. Early postnatal dexamethasone was used in 23 of the newborns who developed cPVL (between november 1996 and march 1998). The only antenatal factor associated with cPVL was cardiac decelerations (28% vs 14%, OR = 3.4, 1.1-11.3). The postnatal risk factors were respiratory distress syndrome requiring the use of rescue surfactant (78% vs 38%, OR = 4.2, 1.4-11.9) and early postnatal dexamethasone at the time it was used (78% vs 17%, OR = 17.1, 3.9-73). CONCLUSION: The use of rescue surfactant and of early postnatal dexamethasone in preterm infants with respiratory distress syndrome were independently associated with the subsequent occurrence of cPVL. Cardiac deceleration was the only antenatal factor associated with cPVL.     

Mechanical ventilation in preterm infants: neurosonographic and developmental studies.

Surviving preterm infants of less than 34 weeks' gestation who were selected on the basis of serial cranial ultrasonographic findings during their nursery course had repeated neurologic and developmental examinations during late infancy and early childhood that established the presence (n = 46) or absence (n = 205) of spastic forms of cerebral palsy. Of the 205 infants without cerebral palsy, 22 scored abnormally low on standardized developmental testing during early childhood. The need for mechanical ventilation beginning on the first day of life (n = 92) was significantly related to gestational age, birth weight, Apgar scores, patent ductus arteriosus, grade III/IV intracranial hemorrhage, large periventricular cysts, and the development of cerebral palsy. In the 192 mechanically ventilated infants, vaginal bleeding during the third trimester, low Apgar scores, and maximally low PCO2 values during the first 3 days of life were significantly related to large periventricular cysts (n = 41) and cerebral palsy (n = 43), but not to developmental delay in the absence of cerebral palsy (n = 18). The severity of intracranial hemorrhage in mechanically ventilated infants was significantly associated with gestational age and maximally low measurements of PCO2 and pH, but not with Apgar scores or maximally low measurements of PO2. Logistic regression analyses controlling for possible confounding variables disclosed that PCO2 values of less than 17 mm Hg during the first 3 days of life in mechanically ventilated infants were associated with a significantly increased risk of moderate to severe periventricular echodensity, large periventricular cysts, grade III/IV intracranial hemorrhage, and cerebral palsy. Neurosonographic abnormalities were highly predictive of cerebral palsy independent of PCO2 measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

脑性瘫痪儿童的MRI特征

目的 探讨脑性瘫痪(脑瘫)患儿脑MR／的表现及其与出生胎龄和脑瘫类型的关系。方法 回顾性分析104例脑瘫患儿的病史、l临床与MR／表现。结果 早产与足月儿脑瘫类型构成显著不同,早产儿以痉挛性双瘫多见(占66．O％),而足月儿偏瘫和失调型高于早产儿。104例脑瘫患儿MR／异常率为84．7％,早产和足月儿组MHI异常率差异无显著性。痉挛型双瘫、四肢瘫、偏瘫、手足徐动型和失调型脑瘫MR／异常率分别为89．4％、100％、100％、54．5％和90．O％。31／42例痉挛性双瘫表现为脑室周围白质软化症(PVL),而以早产儿双瘫更多见(90％);各类型脑瘫的MR／异常表现不同,双瘫以PVL为主,徐动型表现为基底节病变或．PVL失调型绝大部分存在先天性小脑发育不全,偏瘫型突出表现为单侧脑损伤。出生胎龄与MRI特点有关,早产儿组以PVL为特征,见于除失调型外的其他脑瘫类型;足月儿脑瘫MR／异常表现变化多且病变广泛。结论MR／有助于评价各型脑瘫的病理特点及其与出生胎龄的关系．对脑瘫病因的推测有帮助。     

Motor skills in extremely low birthweight children at the age of 6 years.

Fifty three children aged 6 years old who had weighed less than 1251 g at birth without cerebral palsy and receiving mainstream education, were entered into a controlled study of motor skills. The index and control children were matched by age, sex, and school. The index group were considered by their teachers to have similar academic performances to their index group were considered by their teachers to have similar academic performances to their controls, although two index cases were receiving remedial teaching. On the test of motor impairment extremely low birthweight children had significantly more motor difficulties than controls. In addition, the index group had more minor neurological signs, lower intelligence quotients, and more adverse behavioural traits. The higher motor impairment scores among index children were independent of differences in intelligence quotient between the two groups. There was no association between impairment score and the presence or degree of periventricular haemorrhage or periventricular leucomalacia on neonatal cerebral ultrasound. Children with Apgar scores at five minutes of less than 7 had significantly higher impairment scores compared with those whose scores were 7 or more. Three perinatal factors (Apgar score at five minutes, neonatal septicaemia, and abnormal movements) explained 32% of the variance in impairment score at the age of 6 years. In children who do not have cerebral palsy perinatal factors may still be important in the development of motor skills. The presence of subtle neuromotor impairments at 6 years of age has implications for schooling that need further evaluation.     

足月儿早产儿痉挛型脑性瘫痪CT的对比研究

目的：研究足月儿与早产儿痉挛型脑性瘫痪的CT表现。方法：回顾性分析88例痉挛型脑性瘫痪患儿CT表现,分早产儿和足月儿两组分析,其中46例足月儿,42例早产儿。结果：88例痉挛型脑性瘫痪患儿CT表现的阳性率78.4%(69/88)。主要是脑室周围白质软化(PVL)后遗改变,为47/88例,其中足月儿17例,早产儿30例,两组差异有显著性意义(P<0.05);PVL白质减少可发生于侧脑室体中前部、侧脑室体后部、侧脑室三角区、半卵圆中心,两组间白质减少和侧脑室扩大部位差异无显著性意义;而侧脑室形态不规则扩大在早产儿30例中有7例,足月儿侧脑室扩大未见不规则改变,两组差异有显著性意义(P<0.05)。结论：痉挛型脑性瘫痪CT主要表现为PVL后遗改变,早产儿出现PVL和重度PVL的概率明显大于足月儿。     

Hypocarbia in the ventilated preterm infant and its effect on intraventricular haemorrhage and bronchopulmonary dysplasia

OBJECTIVE: To examine the relationship between PaCO2 levels in ventilated very preterm infants and (i) the incidence of severe intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL); and (ii) bronchopulmonary dysplasia (BPD). METHODS: A retrospective cohort analysis of preterm infants comparing PaCO2 levels with the incidence of severe IVH/PVL and BPD was carried out on patients born at less than 29 weeks gestation from 1992 to 1994 and admitted to the tertiary neonatal intensive care unit at the King Edward Memorial Hospital (314 infants). During the first 96 h, PaCO2 levels were examined including lowest and highest PaCO2 levels, mean PaCO2 levels and duration of hypocarbia both pre- and post-surfactant administration. RESULTS: Of the 314 infants, there were 40 early neonatal deaths (less than 48 h) who were not included in the analysis. Of the 274 surviving infants, 72 (26%) infants had severe IVH. Infants whose PaCO2 fell below 30 mmHg at any stage in the first 48 h of life had an increased risk of severe IVH or PVL (odds ratio 2.38; 95% CI 1.27-4.49; P = 0.007). Of the 265 survivors to 36 weeks corrected gestational age, 134 (51%) had BPD. Infants with at least three PaCO2 values less than 30 mmHg in the first 24 h of life had an increased risk of BPD (odds ratio 2.21; 95% CI 1.05-4.57; P = 0.036). CONCLUSIONS: The risk of severe IVH/PVL was significantly increased by hypocarbia. There was also an association between hypocarbia and BPD, particularly when hypocarbia was prolonged. These findings suggest that avoidance of hypocarbia may reduce the incidence of severe IVH/PVL and BPD in preterm infants.     

Possible Etiological Factors in Extensive Periventricular Leukomalacia of Preterm Infants

ABSTRACT. During a twelve-month period five cases of extensive periventricular leukomalacia (PVL) in preterm infants with a gestational age of 31–32 weeks were diagnosed by routine ultrasound screening of preterm infants. The perinatal courses and later development of these infants were compared with 12 other infants with a comparable gestational age born during the same time period. PVL babies were delivered more often by the vaginal route ( p =0.0034), and their mean highest serum total bilirubin value was significantly higher ( p =0.0054) than that of the control infants. The mean value of the highest blood pH during the first 72 hours of life was also significantly higher ( p =0.0311) in PVL babies than in control babies. On the basis of these results we speculate that in addition to ischaemia in the periventricular area, bilirubin toxicity may play an additional role in the severe damage seen in extensive periventricular leukomalacia.     

Correlation between neuroimaging and neurological outcome in periventricular leukomalacia: Diagnostic criteria

BACKGROUND: Periventricular leukomalacia (PVL) is the most important factor in cerebral palsy in preterm infants. METHODS: In the present study, we investigated 747 preterm infants of less than 36 weeks gestation who were repeatedly examined by cranial ultrasonography and computed tomography (CT) scanning at around 40 weeks of corrected post-menstrual age. The clinical course of these infants was followed for more than 3 years and they were examined by magnetic resonance imaging (MRI) between 12 and 18 months of age. RESULTS: Single examinations in early infancy were not sufficient to diagnose PVL, but the combination of ultrasonography, CT and MRI examinations allowed the clinical diagnosis of PVL. In preterm infants, clinical PVL could be predicted from cystic PVL and periventricular echogenicity (PVE) 3 or PVE 2 prolonged over 3 weeks on ultrasonography and confirmed by MRI after 11 months of corrected age. CONCLUSIONS: We tried to determine diagnostic criteria for PVL by neuroimaging. Such criteria from neuroimaging for PVL may be useful for determining the exact occurrence rate of and clinical risk factors for PVL.     

Does perinatal hypocarbia play a role in the pathogenesis of cerebral palsy?

This study aimed to evaluate the role of hypocarbia as a risk factor for mortality and for cerebral palsy in extremely low birthweight infants. The records for 215 extremely low birthweight children were analysed, grouping the infants into those who died (n = 72), those who had a confirmed diagnosis of cerebral palsy (n = 27) and those without major neurological symptoms at the age of 2 y (n = 116). The analysed risk factors were: birthweight, gestational age, maternal diseases and toxaemia, multiple pregnancy, male gender, respiratory distress syndrome, abnormal neonatal cerebral ultrasound, occurrence of septic infection, and/or at least one episode of systemic hypotension and/or at least two episodes of hypocarbia (<3 kPa) during the neonatal period. The mortality rate was 31% and the rate of cerebral palsy was 17% in the survivors. Hypocarbia was found in 33% of children with cerebral palsy, in 10% of infants who died and in 19% of the healthy controls; the differences were statistically insignificant. Birthweight and gestational age, episodes of systemic hypotension and abnormal ultrasound emerged as risk factors for mortality. Abnormal cerebral ultrasound was the only significant risk factor for cerebral palsy. The role of hypocarbia in the pathogenesis of CP remained indistinct but the distribution of risk factors was different in infants with a mortal outcome and in infants with cerebral palsy.     

Possible etiological factors in extensive periventricular leukomalacia of preterm infants

During a twelve-month period five cases of extensive periventricular leukomalacia (PVL) in preterm infants with a gestational age of 31-32 weeks were diagnosed by routine ultrasound screening of preterm infants. The perinatal courses and later development of these infants were compared with 12 other infants with a comparable gestational age born during the same time period. PVL babies were delivered more often by the vaginal route (p = 0.0034), and their mean highest serum total bilirubin value was significantly higher (p = 0.0054) than that of the control infants. The mean value of the highest blood pH during the first 72 hours of life was also significantly higher (p = 0.0311) in PVL babies than in control babies. On the basis of these results we speculate that in addition to ischaemia in the periventricular area, bilirubin toxicity may play an additional role in the severe damage seen in extensive periventricular leukomalacia.     

Neurodevelopment of preterm infants: neonatal neurosonographic and serum bilirubin studies.

In this study of 249 preterm infants of less than 34 weeks' gestation, the relationships between maximal serum total bilirubin concentrations during the neonatal period, neonatal cranial ultrasonographic abnormalities, and severe neurodevelopmental sequelae are described. The subjects, who were selected on the basis of serial cranial ultrasonographic findings, had repeated neurologic and developmental examinations during late infancy and early childhood that established the presence (n = 45) or absence (n = 204) of spastic forms of cerebral palsy. Of the 204 subjects without cerebral palsy, 23 scored abnormally low on standardized developmental testing during early childhood. All but seven of the subjects with cerebral palsy had grade III/IV intracranial hemorrhage or moderate to severe periventricular echogenicity or both, ultrasonographic abnormalities that probably reflect a disruption in the blood-brain barrier as well as extravasation of blood into brain tissue; however, analysis of the data did not suggest that these cranial ultrasonographic abnormalities increased either the maximum serum bilirubin concentration during the neonatal period or the susceptibility of the subjects to neurologic damage from hyperbilirubinemia. Also, there was no evidence to suggest that bilirubinemia in the range studied (2.3 to 22.5 mg/100 mL total serum bilirubin) was causally related to cerebral palsy, early developmental delay, or the development of periventricular cysts in this population of preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

早产儿脑损伤的危险因素分析

目的 探讨早产儿脑损伤(脑室内出血和脑白质损伤)的危险因素。方法 2014年6月1日至2019年5月31日,在昆明医科大学第一附属医院分娩的出生胎龄28～33+6周的早产儿473例中,入住新生儿科的活产儿443例,排除顽固性低血糖、胆红素脑病、放弃治疗及死亡病例,共纳入392例。结合围产期病史及新生儿早期临床表现,以头颅磁共振成像诊断为主要依据,诊断脑室内出血及脑白质损伤。将患儿分为脑室内出血组(102例)、轻度脑白质损伤组(32例)、中重度脑白质损伤组(31例)及无脑损伤组(227例)。统计学方法采用χ²检验、t检验和Logistic回归模型,分析早产儿不同类型脑损伤的危险因素。结果 392例胎龄28～33+6周的早产儿中,脑损伤发生率为42.1%(165/392),其中脑室内出血发生率为26.0%(102/392),脑白质损伤发生率为16.1%(63/392)。Logistic回归模型显示,脑室内出血的危险因素：重度妊娠期高血压疾病(OR=2.287,95%CI:1.099～4.758,P<0.05)、支气管肺发育不良(OR=2.670,95%CI:1....     

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.