Periventricular Leukomalacia In Infants Research Articles

The impact of neonatal morbidities on child growth and developmental outcomes in very low birth weight infants: a nationwide cohort study

Growth in preterm infants has long-term implications for neurodevelopmental outcomes. We aimed to estimate the nationwide growth outcomes from birth to 5years in infants born under 1500g and to analyze the effects of major morbidities in preterm infants on growth. In total, 2961 children born in 2013 with a birth weight under 1500g who underwent an infant health checkup between 2013 and 2018 according to the National Health Insurance Service database were included. Checkups were conducted at 4-6, 9-12, 18-24, 30-36, 42-48, and 54-60months of age. Information was obtained from the International Classification of Diseases-10 codes or a questionnaire administered during the check-up. At 60months of age, the mean percentiles of weight, height, and head circumference fell within only the 30-40th percentile of normal growth values. About 30% of infants had growth parameters below the 10th percentile and showed worse neurodevelopmental outcomes. Using multiple logistic regression, infants with bronchopulmonary dysplasia showed a significantly higher incidence of growth restriction in all three categories of weight (odds ratio [OR] 1.50), height (OR 1.33), and head circumference (OR 1.36) at 60months. Sepsis was associated with growth restriction in weight (OR 1.43) and head circumference (OR 1.33). Periventricular leukomalacia infants had relatively small head circumferences (OR 1.91) and poor developmental screening results (OR 2.89).Conclusion: Catch-up growth remains a major issue in infants born under 1500g, especially those with some morbidities from preterm birth. Regular checkups to monitor and early intervention to achieve normal growth are essential. What is Known: • Growth in preterm infants has long-term implications for neurodevelopmental and cardiometabolic outcomes. • Data are lacking on the time-serial effects of many preterm morbidities simultaneously on long-term growth outcomes. What is New: • All growth parameters of VLBW infants, including weight, height, and head circumference, fell within the 30-40th percentile of normal growth for infants at 60 months of age, indicating that catch-up growth for VLBW infants remains an issue. • VLBW infants with major preterm morbidities, including BPD, PVL, and sepsis, showed difficulties in achieving normal catch-up growth and neurodevelopment at 60 months of age.

Scoring system for periventricular leukomalacia in infants with congenital heart disease.

Currently two magnetic resonance imaging (MRI) methods have been used to assess periventricular leukomalacia (PVL) severity in infants with congenital heart disease: manual volumetric lesion segmentation and an observational categorical scale. Volumetric classification is labor intensive and the categorical scale is quick but unreliable. We propose the quartered point system (QPS) as a novel, intuitive, time-efficient metric with high interrater agreement. QPS is an observational scale that asks the rater to score MRIs on the basis of lesion size, number, and distribution. Pre- and postoperative brain MRIs were obtained on term congenital heart disease infants. Three independent observers scored PVL severity using all three methods: volumetric segmentation, categorical scale, and QPS. One-hundred and thirty-five MRIs were obtained from 72 infants; PVL was seen in 48 MRIs. Volumetric measurements among the three raters were highly concordant (ρc = 0.94-0.96). Categorical scale severity scores were in poor agreement between observers (κ = 0.17) and fair agreement with volumetrically determined severity (κ = 0.26). QPS scores were in very good agreement between observers (κ = 0.82) and with volumetric severity (κ = 0.81). QPS minimizes training and sophisticated radiologic analysis and increases interrater reliability. QPS offers greater sensitivity to stratify PVL severity and has the potential to more accurately correlate with neurodevelopmental outcomes.

Relation between prognosis and changes of MBP and S100B in premature infants with periventricular leukomalacia.

This study aims to explore the relation between changes in myelin basic protein (MBP) and S100 protein (S100B) serum levels and prognosis in premature infants with periventricular leukomalacia (PVL). In our hospital, 78 premature infants with PVL and 43 normal premature infants were studied from July 1, 2007 to December 31, 2008. MBP and S100B serum levels were detected at 1, 3, 7, and 14 days after birth by using enzyme-linked immunosorbent assay. All infants were followed four times (once every 3 months) after discharge from hospital. Their intelligence quotient and physical development index were tested by using Gesell developmental scales. The MBP serum levels were significantly higher in premature infants with PVL at any time point than in normal premature infants. S100B serum levels gradually increased at 1, 3, and 7 days; peaked on the 7th day; and then gradually decreased to the normal level on the 14th day. The intelligence quatient and physical development index of infants with increased S100B and MBP levels on the 7th day were lower than those of infants who had normal S100B and MBP levels and those of normal premature infants. A negative relation exists between S100B and MBP serum levels and prognosis in PVL infants. An increase of MBP and S100B levels lasting >7 days could cause poor prognosis.

Acute and massive bleeding from placenta previa and infants' brain damage

BackgroundAmong the causes of third trimester bleeding, the impact of placenta previa on cerebral palsy is not well known. AimsTo clarify the effect of maternal bleeding from placenta previa on cerebral palsy, and in particular when and how it occurs. Study designA descriptive study. SubjectsSixty infants born to mothers with placenta previa in our regional population-based study of 160,000 deliveries from 1998 to 2012. Premature deliveries occurring at<26weeks of gestation and placenta accreta were excluded. Outcome measuresPrevalence of cystic periventricular leukomalacia (PVL) and cerebral palsy (CP). ResultsFive infants had PVL and 4 of these infants developed CP (1/40,000 deliveries). Acute and massive bleeding (>500g within 8h) occurred at around 30–31weeks of gestation, and was severe enough to deliver the fetus. None of the 5 infants with PVL underwent antenatal corticosteroid treatment, and 1 infant had mild neonatal hypocapnia with a PaCO2 <25mmHg. However, none of the 5 PVL infants showed umbilical arterial acidemia with pH<7.2, an abnormal fetal heart rate monitoring pattern, or neonatal hypotension. ConclusionsOur descriptive study showed that acute and massive bleeding from placenta previa at around 30weeks of gestation may be a risk factor for CP, and requires careful neonatal follow-up. The underlying process connecting massive placental bleeding and PVL requires further investigation.

Relationship between enlargement of the lateral ventricle and periventricular leukomalacia in infants

To examine if we could predict periventricular leukomalacia (PVL) from the area of the lateral ventricle (LV). Six neonates in whom cystic PVL could be detected by magnetic resonance imaging (MRI) but not by ultrasound (US) were termed the 'invisible group'. Six neonates in whom cystic PVL could be detected by MRI and US were termed the 'visible group'. Eleven neonates in whom cystic PVL could not be detected by MRI or US were termed the 'control group'. The ratio of LV to head circumference (HC) was calculated as the area of LV (cm²)/HC (cm) × 100. Receiver operating characteristic (ROC) curve analysis was carried out to find the cutoff value. There were no significant differences among the three groups with respect to gestational age, birthweight, postnatal age and HC. The ratio of LV to HC in the control group was a median value of 0.38, it was 0.79 in the invisible group, and 0.96 in the visible group. The ratio was significantly higher in the visible group (P < 0.001) and in the invisible group (P < 0.05) than in the control group. This ratio was low in the two infants who had PVL only in the collateral trigone. The ROC curve suggested a cutoff value of 0.6 (sensitivity 79.17%, specificity 100%) to suspect PVL. We may need to suspect PVL in infants whose lateral ventricle is enlarged even if cystic PVL is not detected by ultrasound. PVL present only in the collateral trigone needs to be evaluated using cerebral MRI.

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

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. 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. 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. 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.

Relationship between serum lactate level and periventricular leukomalacia

In a case control study, we evaluated the serum lactate levels during the early days of life in preterm infants with periventricular leukomalacia (PVL), who were presumed to have suffered injury around birth. Thirteen infants diagnosed by ultrasonography as suffering from cystic PVL during the neonatal period and 26 normally developed infants matched by gestational age were enrolled in the study. The serum lactate level was measured repeatedly during the 72 h after birth. The mean serum lactate levels on admission were 2.95 ± 0.43 and 3.21 ± 0.29 mmol/L in the PVL and control groups, respectively. There was no statistically significant difference in the serum lactate level between the groups at any point during the first 72 h after birth. In conclusion, the serum lactate level was not elevated in preterm infants with PVL suggesting that the serum lactate level is not a useful predictor for the development of PVL in infants.

MEK-ERK Signaling Is Involved in Interferon-γ-induced Death of Oligodendroglial Progenitor Cells*♦

Oligodendrocytes are exposed to various cytokines in inflammatory lesions in the central nervous system. In this study, we focused on the direct effects of interferon-gamma (IFNG) on highly purified rat oligodendroglial cultures at different developmental stages. Among the three stages tested, IFNG had direct cytotoxic effects on actively proliferating oligodendrocyte progenitors but much less on immature oligodendrocytes and none on mature oligodendrocytes. This stage-specific susceptibility of progenitors to IFNG-induced cytotoxicity consisted of two components, delay in the G(1)/S transition of the cell cycle and increased cell death at least partly mediated by apoptosis, suggesting that progression of the cell cycle was tightly linked to this toxic mechanism. There was no functional difference in the signal transducers and activators of transcription (STAT) pathways between progenitors and mature oligodendrocytes as determined by induction of IRF1 mRNA in response to IFNG. We found that partial inhibition of the MEK-ERK pathway, one of the mitogen-activated protein kinase phosphorelay modules, by U0126 partially reversed the IFNG-induced cytotoxicity in progenitors. In addition, ERK activity was quickly down-regulated after in vitro differentiation of progenitors to immature oligodendrocytes. Therefore, we concluded that simultaneous activation of the STAT pathway by IFNG and of the ERK pathway by exogenous trophic factors played a role in the stage-specific IFNG-induced cytotoxicity in oligodendroglial progenitors. Our study has implications with respect to the mechanisms of periventricular leukomalacia in infants and of persistent demyelination in multiple sclerosis lesions in adults.

Periventricular Leukomalacia with Late-Onset Circulatory Dysfunction of Premature Infants: Correlation with Severity of Magnetic Resonance Imaging Findings and Neurological Outcomes

The incidence of late-onset circulatory dysfunction (LCD) of premature infants, which is characterized by sudden hypotension and oliguria, has recently increased in Japan. This condition suddenly occurs after several days of age without obvious causes in preterm infants with stable respiration and circulation. Intravenous steroids frequently improve the hypotension. The main problem with LCD is the subsequent and frequent onset of periventricular leukomalacia (PVL), and neurological development appears to be worse in PVL patients with LCD than those without LCD. The aim of this study was to determine whether the severity of magnetic resonance imaging (MRI) findings and neurological outcomes differ between infants who developed PVL after LCD and those who developed PVL without LCD. We retrospectively studied preterm infants who were delivered at less than 33 weeks of gestation between the years 2000 and 2003. During the study period, 10 and 26 infants developed PVL with and without LCD, respectively. The incidence of severe or moderate MRI findings was significantly higher in PVL patients with LCD (100%) than those without LCD (50%; p < 0.05). The incidence of severe cerebral palsy was 88% in PVL infants with LCD and 43% in PVL infants without LCD (p < 0.05). Moreover, the incidence of visual disorders was significantly higher in PVL infants with LCD (63%) than those without LCD (9%; p < 0.01). In conclusion, neurological outcomes are worse in preterm infants who develop PVL with LCD than those without LCD, which is well correlated to the severity judged by MRI findings.

Early Gastrointestinal Function and Nutritional Status in Preterm Infants with Cystic Periventricular Leukomalacia

Objective: To retrospectively investigate the early gastrointestinal function and the nutritional status of very low birth weight (VLBW) infants with cystic periventricular leukomalacia (PVL). Methods: Sixty-five VLBW infants who were admitted to Kakogawa Municipal Hospital were divided into 2 groups: 5 infants were in the PVL group, and the remaining 60 infants were in the normal group. The gastrointestinal function of the infants in the early neonatal period was compared between the 2 groups using an analysis of gastric aspirates and abdominal radiographs, and pulsed-Doppler ultrasonographic measurement of the flow velocity in the superior mesenteric artery (SMA). Results: In the first week, there were more days in which abdominal gastric residual fluids occurred in the PVL group than in the normal group. The occurrence of abnormal findings in the abdominal radiograph within the first 7 days was significantly higher in the PVL group than in the normal group. Longitudinal ultrasonographic comparisons of the SMA flow velocity showed that the mean values in peak systolic velocity and in time-averaged velocity were both significantly higher in the PVL group than in the normal group before 7 days of life. Both the total volume of milk ingested and the total energy intake in the PVL group were significantly lower than in the normal group within the first 2 weeks of life. Conclusions: Despite the low number of infants with PVL, we may suggest that the gastrointestinal function of the preterm infants with cystic PVL may deteriorate significantly compared to normal infants in the early neonatal period of life, and consequently, the early nutritional intakes in the PVL infants are inferior to those in the normal infants.

Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights

Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights

Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights

Fifteen appropriate-for-date premature low-birthweight infants with cystic periventricular leukomalacia (PVL) were studied. The infants were stratified into three birthweight groups: less than 1000 g, 1000 g and greater but less than 1500 g, and 1500 g or greater. Reported and new risk factors for PVL were compared with control patients for all patients and each birthweight group. Hypocarbia was significantly related to cystic PVL, especially in infants with birthweight 1000 g or greater (p < 0.03). Sensitivity to hypocarbia might be decreased in infants with birthweight less than 1000 g due to therapy or prematurity. In the group with birthweight less than 1000 g, the proportion of cystic PVL infants on continuous intra-arterial blood-pressure monitoring tended to be lower than the controls, with an almost significant difference (p= 0.05). The duration of tocolysis was significantly longer in the cystic PVL infants than in the controls when the birthweight was greater than 1500 g (p < 0.04). For some risk factors, a significant difference or a tendency of difference was demonstrated only after stratifying the birthweight. For others, the difference became insignificant after stratification. Assessing risk factors after stratifying by birthweight or degree of prematurity is therefore useful. Conclusion: The results suggest that hypocarbia should be avoided to prevent cystic PVL, especially in infants with birthweight of 1000 g or greater, continuous intra-arterial blood-pressure monitoring may be important in infants with birthweight less than 1000 g, and fetal status should be monitored carefully when the duration of tocolysis is prolonged, especially in infants with birthweight of 1500 g or more.

Significance of clinical risk factors of cystic periventricular leukomalacia in infants with different birthweights

Fifteen appropriate-for-date premature low-birthweight infants with cystic periventricular leukomalacia (PVL) were studied. The infants were stratified into three birthweight groups: less than 1000 g, 1000 g and greater but less than 1500 g, and 1500 g or greater. Reported and new risk factors for PVL were compared with control patients for all patients and each birthweight group. Hypocarbia was significantly related to cystic PVL, especially in infants with birthweight 1000 g or greater (p < 0.03). Sensitivity to hypocarbia might be decreased in infants with birthweight less than 1000 g due to therapy or prematurity. In the group with birthweight less than 1000 g, the proportion of cystic PVL infants on continuous intra-arterial blood-pressure monitoring tended to be lower than the controls, with an almost significant difference (p = 0.05). The duration of tocolysis was significantly longer in the cystic PVL infants than in the controls when the birthweight was greater than 1500 g (p < 0.04). For some risk factors, a significant difference or a tendency of difference was demonstrated only after stratifying the birthweight. For others, the difference became insignificant after stratification. Assessing risk factors after stratifying by birthweight or degree of prematurity is therefore useful. The results suggest that hypocarbia should be avoided to prevent cystic PVL, especially in infants with birthweight of 1000 g or greater, continuous intra-arterial blood-pressure monitoring may be important in infants with birthweight less than 1000 g, and fetal status should be monitored carefully when the duration of tocolysis is prolonged, especially in infants with birthweight of 1500 g or more.

Risk Factors for Cystic Periventricular Leukomalacia in Very-Low-Birth-Weight Infants † 1232

Cystic periventricular leukomalacia (PVL) occurs most commonly in very-low-birth-weight (VLBW, <1500 gm) infants and is associated with poor developmental outcome. Ischemia has been implicated in the pathogenesis of PVL and recently intrapartum magnesium sulfate (MAG) treatment has been suggested to be neuroprotective; however, clinically relevant risk factors and preventive measures for PVL in VLBW infants remain unclear. We performed a retrospective, matched case-control study of the predictors of PVL in all infants <1500 gm BW from 6/90 to 12/95, during which early and late sonographic screening was routine. We studied anteparum, intrapartum, and postnatal factors, concentrating on vascular, respiratory, and infectious factors, and on intrapartum MAG exposure. We identified 1417 VLBW infants and 54 cases of cystic PVL (inc. 3.8%) and matched 54 controls with normal sonograms (latest at least 30 days) for ±150 gm BW and date of birth. Controls and cases were similar in mean BW (978±234 vs 945±250gm) and gestational age (28±2 wks). PVL cases were more likely to be outborn (37% vs 19%), to have a rapid(≤3 hrs) period from rupture of membranes (ROM) to birth (62% vs 41%), to have a patent ductus arteriousus (60% vs 37%), and to have a higher max PaCO2 in the first 72 hrs (55±16 vs 48±16) and were less likely to have pre-eclampsia (4%vs 15%) (all P≤0.05). The proportions of any intrapartum MAG, tocolytic MAG, steroid use, chorioamnionitis, SGA, RDS, and indomethacin use were similar. When controlled for indomethacin use, MAG use, PaCO2, and delivery location, a logistic regression model determined that predictors for PVL were as in Table. We conclude that PDA and rapid labor course are risk factors for PVL and that pre-eclampsia is more important than MAG use in reducing brain injury.

The evolution and outcome of cavitating periventricular leukomalacia in infants

The evolution and outcome of cavitating periventricular leukomalacia in infants

The evolution and outcome of cavitating periventricular leukomalacia in infants

The evolution and outcome of cavitating periventricular leukomalacia in infants