Incidence Of Periventricular Leukomalacia Research Articles

Effect of duration of delayed cord clamping on serum bilirubin hematocrit and hemodynamic status in neonates

Introduction:DCC is a common practice with several benefits. The benefits of DCC are decreased risk of anemia, less incidence of periventricular leukomalacia, less incidence of NEC. This study tries to compare the effect of different duration of delayed cord clamping on serum bilirubin, hematocrit and hemodynamic status of a neonate. Material and method:A prospective study was done over a span of one year comprising of 150 full term neonates. After obtaining consent prior before delivary females who met the inclusion criteria were randomly assigned to 3 groups.For group 1 the cord was clamped at a duration of 30 sec, 60 sec for group 2 and 120 sec for group 3. Exact time of delayed clamping was recorded using a stop watch. Serum bilirubin and hematocrit level and parameters like respiratory rate, pulse rate, capillary refill time and temperature was assessed at day three. Results: Group 1 showed a mean hematocrit % of 41.51 (SD 10.28). Group 2 showed mean hematocrit % of 45.11 (9.4) and mean hematocrit % of group 3 was 45.64 (8.37).

Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis.

BackgroundAt present, the conclusions about the impact of hypertensive disorders of pregnancy (HDP) on the clinical outcomes of preterm infants are inconsistent. This study used the propensity score matching (PSM) analysis to evaluate the effect of HDP on clinical outcomes of extremely preterm or extremely low birth weight (EP/ELBW) infants.MethodsRetrospective analysis was performed on the EP/ELBW infants discharged from 26 tertiary neonatal intensive care units or died during hospitalization from 2008 to 2017, who were divided into HDP group and non-HDP group. The six covariates including sex, gestational age, birth weight, twin or multiple pregnancy, antenatal steroids administration, and conception method were matched through the PSM method at a ratio of 1:1. The survival rate at discharge and the major clinical complications were compared between the two groups.ResultsAfter matching the six covariates, compared with the non-HDP group, there was no significant difference in the survival rate at discharge (64 vs. 63.2%, p > 0.05), the incidence of bronchopulmonary dysplasia (BPD) or moderate to severe BPD in the HDP group (58.3 vs. 54.9%, p > 0.05; 5.2 vs. 6.2%, p > 0.05). The incidence of periventricular leukomalacia (PVL) in the HDP group was significantly increased (5.7 vs. 1.9%, p < 0.05).ConclusionsHDP increased the risk of PVL in EP/ELBW infants, but had no significant effect on the survival rate at discharge, or the occurrence of other complications.

Neonatal seizure caused by periventricular leukomalacia resulting from maternal protein S deficiency and treated with aspirin

Periventricular leukomalacia (PVL) is a white matter injury that mostly occurs with prematurity at the gestational age (GA) of 24–32 weeks and birth weight below 1500 g. A major cause of PVL is neonatal hypoxic ischemia and/or hemorrhage around the ventricles of the brain, which could lead to neonatal seizure.1 The incidence of PVL in preterm infants declines with increasing GA.2 This report presents the case of a near-term neonate at GA of 36 4/7 weeks who had neonatal seizure at the age of 1.5 months and whose brain image showed significant bilateral PVL.

Evaluation of the relationship between cranial magnetic resonance imaging findings and clinical status in children with cerebral palsy

Background/aimThe objective of this study was to evaluate the relationship between cranial magnetic resonance imaging (MRI) findings and clinical features in cerebral palsy (CP).Materials and methodsChildren aged 3 to 18 years, who were followed with the diagnosis of CP between January 2012 and September 2015, were included. The type of CP was classified using the European Cerebral Palsy Monitoring Group’s classification system and then, patients were divided into two groups as spastic or nonspastic groups. The Gross Motor Function Classification System (GMFCS) was used to determine the level of mobility. According to the GMFCS, levels 1, 2, and 3 were grouped as mobile, and levels 4 and 5 were grouped as immobile. Cranial MRI findings were reevaluated by a voluntarily radiologist and grouped as periventricular leukomalacia (PVL) (grades 1, 2, and 3), cerebral atrophy, migration anomaly, cerebellar involvement, basal ganglion involvement, and normal MRI findings.ResultsSixty-two patients were enrolled. The rate of mobile patients did not differ between the spastic and nonspastic groups. The incidence of PVL was significantly higher in cases of prematurity and spastic CP ( p < 0.05). The rate of mobilization was significantly lower and the rate of epilepsy was significantly higher in patients with PVL. Immobile patients were more common among cases of grade 3 PVL ( p < 0.05). Conclusion The most common cranial MRI pathology was PVL, and the presence of PVL and its grade might help clinically assess the patient’s CP type and level of mobilization. While pathology was observed mostly in cranial MRI in cases of CP with similar clinical features, the fact that cranial MRI was completely normal for 14.5% of the cases suggests that there may be some pathologies that we could not identify with today’s imaging technology.

Incidence of periventricular leukomalacia in preterm very low birth neonates – A tertiary care experience

Background: The periventricular leukomalacia (PVL) is the most common white matter injury in preterm very low birth weight (VLBW) neonates. It occurs due to ischemic injury to developing oligodendrocytes. It can be detected by cranial ultrasonography (CUS). Objective: The objective of the study was to find incidence of PVL in preterm VLBW babies and its correlation with gestational age, birth weight, and arterial blood PH. Materials and Methods: A total of 80 preterm low birth babies admitted in our neonatal intensive care unit over 1 year were included who met the inclusion criteria. All babies were subjected to CUS starting from the 1st week of their life and repeated weekly by trained radiologist to find changes suggestive of PVL till clinically indicated or normal scan on the 14th day of life. Results: Among 80 preterm low birth babies in our study, 54 (67.5%) were male and 26 (32.5%) were female. Three babies had gestational age of 30 weeks or less, 25 had gestational between 30 and 32 weeks, 35 had gestational age between 32 and 34 weeks, while 17 had gestational age more than 34 weeks. A total of 62 (77.5%) were born through normal vaginal delivery and 18 (22.5%) were born by cesarean section. The incidence of PVL was 2.5%. The most common change was periventricular flare. The incidence of PVL was more in extreme preterm and those with PH &lt;7.2. The mortality was 50% in babies with PVL. Conclusion: The incidence of PVL in preterm low birth weight babies is 2.5% with a mortality of 50%. Prevention and early detection are the keys to mitigate the effects of this disastrous complication of prematurity.

Neurodevelopmental impairment in necrotising enterocolitis survivors: systematic review and meta-analysis

AimTo determine (1) the incidence of neurodevelopmental impairment (NDI) in necrotising enterocolitis (NEC), (2) the impact of NEC severity on NDI in these babies and (3) the cerebral lesions found...

Using of sustained lung inflation method in newborn suffering with RDS during their stabilization in delivery room

Using of sustained lung inflation (SLI) during newborn stabilization in delivery room, as a new strategy of therapy in newborn with RDS. The aim: to study the efficiency of sustained lung inflation (SLI) during stabilization in delivery room in the very preterm in infants suffering from respiratory distress syndrome (RDS). Material and methods: 122 infants born 23.01.2012 to 07.09.2014 in Zhytomir Oblast Perinatal Center. The infants were 28,2 ± 1.9 weeks old, weighed 1097 [540 - 1500] g., and had the clinical signs of RDS. Two group of infant were observed: a group of newborn (n = 68, index group), was provided of sustained lung inflation (SLI) during stabilization in delivery room and control group (n = 54), without using sustained lung inflation (SLI) during stabilization. All the newborns were administered surfactant replacement therapy with the help of Curosurf® by the technique of minimally invasive surfactant treatment (MIST) on the background of “lungs involvement”. The both methods were compared and tested for death, IVH, PVL, BPD, pneumothorax frequency. The investigation is done within the framework of comparison with historical control. Results: no complications were observed during using of sustained lung inflation in delivery room in the very preterm in infants suffering from respiratory distress syndrome. The infants tolerated the administration well. The investigation revealed no increase in duration of oxygen therapy in the infants of index group versa those of control group. The comparison of using SLI in delivery room and not using SLI in delivery revealed difference in duration of primary ventilator support, so the need of mechanical ventilation in index group were less versa control group: 50.0% newborn needed only CPAP therapy versa 38.9% newborn (р = 0,29). The research detected tendency to more less of duration of CPAP therapy in index group (p = 0.07). The investigation revealed no statistical discrepancy in the developmental frequency of severe BPD in the number of the infants who undergoing SLI in delivery room and in the number of newborn with standard method of stabilization in delivery room: 11.8% vs. 9.3%, accordingly (p=0,88), in severe IVH: 7.4% vs. 7.4.%, accordingly (p=0,73), incidence of periventricular leukomalacia: 4.4% versa 1,9%, accordingly (р = 0,79), in the incidence of air leak syndrome: 1.5% versa 1.9%, accordingly (р = 0,59). The observation revealed no statistical discrepancy in death or BPD frequency in the infants (weighed from 500 till 999 g) of the index group versa those of the control group (accordingly 58.6% versa 42.9%, (р = 0,42); in severe IVH and BPD: 13.8% vs. 9.5.%, accordingly (p=0,98) and 17.2% vs. 9.5.%, accordingly (p=0,72). Using of sustained lung inflation (SLI) during newborn stabilization in delivery room, which needed surfactant-replacement therapy, doesn’t have any positive effect compare with newborn in standard treatment: using PPV (positive pressure ventilation). Further investigations to study the clinical efficacy of sustained lung inflation (SLI) during newborn stabilization in delivery room are needed especially in newborn less 28 weeks gestation age.

Placental histologic patterns and neonatal seizure, in preterm premature rupture of membrane

Objective: To investigate the relationship between placenta and perinatal outcomes, in preterm infants born to mothers with preterm premature rupture of fetal membrane (PPROM).Methods: We report detailed histology of placentas and perinatal outcomes of infants from 79 PPROM pregnancies. Placental histologic pattern and adverse perinatal outcomes were assessed by logistic regression, adjusting for gestational age at birth, birth weight and interval from rupture of membrane to delivery.Results: Mean gestational age at membrane rupture was 29.5 ± 3.4 weeks. The incidence of histologic chorioamnionitis (HCA), fetal inflammatory response (FIR) and vascular thrombotic abnormalities in placental histologic examination were 63.3, 25.3 and 78.5%, respectively. Neonates with FIR showed significantly higher incidence of periventricular leukomalacia (PVL) (85% versus 59.3%, p = 0.0364) at brain ultrasonography, than neonates without FIR, in univariate analysis, but not in logistic regression analysis. In logistic regression analysis, the odds ratio of low Apgar score at 1 min in the neonates with clinical chorioamnionitis was 5.009 (95% CI, 1.242–20.195). The odds ratio of neonatal seizure in the neonates with FIR and vascular thrombotic problem was 7.486 (95% CI, 1.617–34.653).Conclusions: Our findings support the association between FIR with vascular thrombotic problem in placenta and neonatal seizure, in pregnancies with PPROM.

Relationship between packed red blood cell transfusion and severe form of necrotizing enterocolitis: A case control study

To determine if packed red blood cell transfusion is associated with onset of necrotizing enterocolitis, and whether withholding feed has any association with it. Case records of 100 preterm neonates, (<34 weeks gestation) who developed necrotizing enterocolitis and 99 random age-and gestation-matched controls were evaluated for any blood transfusion 48 h before onset of necrotizing enterocolitis. During the study period 26% infants received packed red blood cell transfusion within 48-hours prior to onset of disease and 84% of these infants were not fed around the time of transfusion. Infants who developed necrotizing enterocolitis after transfusion were older, of lower gestational age, birth weight and more likely to develop stage 3 disease. They had a lower hematocrit at birth and before onset of disease and withholding feeds around transfusion did not prevent necrotizing enterocolitis. Odds of mortality in these infants was 2.83 (95% CI 0.97-8.9) and survivors had no significant difference in incidence of periventricular leukomalacia and length of hospital stay. Blood Transfusion associated necrotizing enterocolitis is a severe, mainly surgical form of disease.

Male Gender Is Associated With Intraventricular Hemorrhage

The goal was to examine the association of gender with intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) in a large national database. The National Inpatient Sample database was analyzed for the years 1998, 1999, 2001, 2002, and 2004 and its pediatrics version for the years 1997, 2000, and 2003. The National Inpatient Sample and its pediatrics version are annually collected databases for inpatient admissions from >1000 hospitals across the United States. We included all very low birth weight (VLBW) infants (birth weight [BW] of <1500 g) and excluded infants with major congenital anomalies. VLBW infants with IVH or PVL were identified by using International Classification of Diseases, Ninth Revision, diagnostic codes. We analyzed the data by using chi(2) and Fisher's exact tests to calculate odds ratios (ORs) and logistic regression analysis to control for possible confounders. The data included 104 847 VLBW infants. With controlling for significant confounders, IVH was associated with male gender (15.9% vs 13.6%; adjusted OR [AOR]: 1.15 [95% confidence interval: 1.11-1.19]; P < .001). More boys than girls had severe IVH (38% vs 32.7%; AOR: 1.18 [95% confidence interval: 1.06-1.32]; P < .004). The increased rates of IVH and severe IVH in boys were significant in the BW subgroups of <1000 g and 1000 to 1499 g. The association of male gender with IVH and severe IVH was more significant in infants of 1000 to 1499 g (AOR: 1.19 vs 1.14; P = .006). The incidence of PVL in VLBW infants was 0.41%, and rates did not differ between genders (0.38% vs 0.43%; P = .42). Compared with girls, VLBW male newborns are at greater risk to develop IVH and severe IVH but not PVL. The association of male gender with IVH or severe IVH is stronger with higher BWs.

Circulatory disturbances during the first postnatal 24 hours in extremely premature infants 25 weeks or less of gestation with histological fetal inflammation

To investigate the effect of pre-existing fetal inflammation on hemodynamics during the first postnatal 24 h in extremely premature infants <or= 25 weeks of gestation. We defined fetal inflammation as the infiltration of neutrophils into the chorionic plate vessels or umbilical cord vessels on histological examination. In 41 infants born between 22 and 25 weeks of gestation, 23 displayed fetal inflammation and 18 displayed no fetal inflammation. Circulatory indices including blood pressure, heart rate, average urine flow, catecholamine index, ejection fraction of the left ventricle, and volume load for 24 h were compared between the two groups, as well as the incidence of intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and death. The comparisons were made with repeated measure anova and with Fisher's exact test, or unpaired t-test. Probability values <0.05 were considered significant. Infants with and without fetal inflammation had similar birthweights and gestational age. There was no significant difference in incidence of PVL and death. However, infants with fetal inflammation had a significantly higher incidence of IVH >or= 3 than infants with no fetal inflammation (49% vs 17%) (P=0.04). Infants with fetal inflammation had significantly higher heart rate (P=0.005), catecholamine index (P=0.019) and volume load (P=0.021). Histological evidence of fetal inflammation in extremely premature infants is associated with circulatory disturbances over the first 24 h of life and increases in the incidence of IVH >or= 3.

Maturation-Dependent Vulnerability of Perinatal White Matter in Premature Birth

Survivors of premature birth have a predilection for perinatal brain injury, especially to periventricular cerebral white matter. Periventricular white matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia) and diffuse myelination disturbances. Recent neuroimaging studies support that the incidence of periventricular leukomalacia is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary but not sufficient to generate the initial injury that leads to PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin-forming oligodendrocytes. There has been substantial recent progress in the understanding of the cellular and molecular pathogenesis of PWMI. The oligodendrocyte progenitor is a key target for preventive strategies to reduce ischemic cerebral white matter injury in premature infants.

Adverse Neonatal Outcomes Associated With Antenatal Dexamethasone Versus Antenatal Betamethasone

For at least 25 years, the delivery of a corticosteroid-usually dexamethasone or betamethasone-has been the most important part of the management of preterm labor at 24 to 34 weeks gestation. Although antenatal corticosteroid treatment has been associated with a significant reduction in respiratory distress syndrome, intraventricular hemorrhage (IVH), and neonatal mortality, both animal and human studies suggest that one of these steroids, dexamethasone, may actually increase the risk of adverse neurologic outcomes. This historical cohort study was an attempt to compare the incidence of periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), IVH, and neonatal mortality in 3600 very-low-birthweight (401-1500 g) infants born after antenatal treatment with betamethasone compared with dexamethasone. A complete course of dexamethasone consisted of 4 6-mg intramuscular doses given at 12-hour intervals and of betamethasone, 2 12-mg intramuscular doses given at a 24-hour interval. Nearly half of the infants (48%) were exposed to betamethasone and 34% to dexamethasone, whereas 18% received no antenatal steroid. The overall rate of PVL was 3.5% and was similar in all 3 groups (4.4% in the no-steroid group, 3.5% in the betamethasone group, and 2.9% in the dexamethasone group; not significant). Infants exposed to either steroid were significantly less likely to have IVH (30.7% in the no-steroid group, 24.4% in the betamethasone group, and 24.8% in the dexamethasone group; P <.05) or severe IVH (12.8% in the no-steroid group, 10.3% in the betamethasone group, and 9.4% in the dexamethasone group; P <.05) than those not exposed to either steroid. Neither steroid changed the risk of severe ROP (8.8% in the no-steroid group, 9.9% in the betamethasone group, and 10.7% in the dexamethasone group), but the overall incidence of ROP was increased in betamethasone-exposed infants (42.9% in the no-steroid group, 46.4% in the betamethasone group, and 42.2% in the dexamethasone group; P <.05). Infants given either steroid were at lower risk of death than those who did not receive antenatal steroids, but betamethasone reduced the risk significantly more than dexamethasone (11.0% in the no-steroid group, 7.4% in the betamethasone group, and 7.9% in the dexamethasone group; P <.05). Odds ratios for all these comparisons were computed by multivariate logistic regression analysis and confirmed the risk reductions. However, when multivariate logistic regression analysis was used to compare the 2 steroid-treated groups with each other, there was only one significant difference; the risk of neonatal death was lower with betamethasone than with dexamethasone (odds ratio, 0.44 for betamethasone vs 0.73 with dexamethasone, P <.05). These and other findings suggest that a randomized clinical trial should be considered to compare the fetal and neonatal effects of dexamethasone and betamethasone. At present, the best management might be to expose very-low-birthweight infants to betamethasone rather than dexamethasone when there is a choice.

Periventricular leukomalacia is common after neonatal cardiac surgery

Objectives Periventricular leukomalacia is necrosis of the cerebral white matter adjacent to the lateral ventricles and results from injury to immature oligodendroglia. In infants without congenital heart disease, periventricular leukomalacia is associated with an increased incidence of developmental delay and attention deficit/hyperactivity disorder. The incidence of periventricular leukomalacia and the risk factors for development of periventricular leukomalacia after infant cardiac surgery are not known. Methods Magnetic resonance imaging of the brain was performed 6 to 14 days after cardiac surgery utilizing cardiopulmonary bypass with or without deep hypothermic circulatory arrest in 105 neonates and infants ≤ 6 months of age. Results Median age at surgery was 6 days (range 1-178), with 82 neonates (age ≤ 30 days). Periventricular leukomalacia was found in 44 of the neonates (54%) compared with 1 of 23 infants (4%). Forward logistic regression using age at surgery as a continuous variable identified a model containing longer total support time (cardiopulmonary bypass plus deep hypothermic circulatory arrest), lower systolic blood pressure at cardiac intensive care unit admission postoperatively, lower minimum diastolic blood pressure, and P o 2 in the first 48 hours after surgery. When age at surgery was considered as a dichotomous variable (neonate versus infant), younger age at surgery replaced systolic blood pressure, P o 2, and total support time in the model. Lower minimum diastolic blood pressure was a significant risk factor in both models. Conclusions Periventricular leukomalacia was found in >50% of neonates after cardiac surgery but rarely in older infants. Hypoxemia and hypotension in the early postoperative period, particularly diastolic hypotension, may be important risk factors for periventricular leukomalacia.

Improved Outcomes for Very-Low-Birthweight Infants: Evidence From a New Zealand National Population-Based Data

The survival chances of very-low-birthweight (VLBW) infants, weighing less than 1500 g, continue to improve, and obstetricians today are more willing to intervene in earlier gestations. Nevertheless, debate continues about the propriety of offering neonatal intensive care for very preterm infants, especially those whose viability is in question. This prospective study compared survival and short-term morbidity in VLBW infants born in New Zealand in 1986 and 1998 through 1999. Data were collected from birth until discharge from the hospital or death. In 1986, 413 VLBW infants, representing 0.78% of live births, were admitted for intensive care. In 1998 through 1999 the number increased to 1084 or 0.96% of all live births, a 31% rise. The proportion of infants weighing 1000 to 1499 g at birth increased 20% from the earlier to the later period, whereas infants weighing 500 to 999 g increased 51%. Survival was significantly higher in 1998 through 1999 for all birth-weight groups, and 38% of 13 infants weighing less than 500 g survived in this period. There was a small reduction in overall median birthweight and gestation in the later period. Fewer infants born in 1998 through 1999 had a 5-minute Apgar score less than 7, and more were exposed to antenatal corticosteroids. There was no substantial difference in the risk of hyaline membrane disease, but more infants in the later period who lived 28 days received assisted ventilation (87% vs. 74% in the earlier group). Chronic lung disease was less frequent in the later period than in 1986, especially in infants weighing 1000 to 1499 g at birth. The same was the case for severe retinopathy of prematurity. The incidence of periventricular leukomalacia was probably higher in 1986. Survival of VLBW infants has improved, significantly in recent years even though more extremely low-birthweight infants are being admitted. At the same time, surviving infants have not experienced more short-term morbidity. Improved regionalization of neonatal intensive care is probably part of the reason, along with the wider use of antenatal steroids, treatments such as exogenous surfactant, and improved technology in the neonatal intensive-care unit.

Dopamine versus dobutamine for hypotensive preterm infants.

Inotropes are widely used in preterm infants to treat systemic hypotension. The most commonly used drugs are dopamine and dobutamine. These agents have different modes of action which may result in different haemodynamic effects. To compare the effectiveness and safety of dopamine and dobutamine in the treatment of systemic hypotension in preterm infants. The standard search method of the Cochrane Neonatal Review Group was used. Searches of electronic and other databases were performed. Previous reviews were searched for references to relevant trials and leading authors in the field were contacted for information about other published and unpublished studies. Randomised controlled trials where short and/or long term effects of treatment with dopamine and dobutamine for the treatment of systemic arterial hypotension were compared were selected for this review. Trials studying newborn infants born before 37 completed weeks gestation and less than 28 days of age were eligible for inclusion. Systemic arterial hypotension was not defined specifically, but accepted as defined in individual studies. Studies were not limited by birthweight, lower gestational age threshold or by route or duration of administration of inotropic agents. Study quality and eligibility were assessed independently by each reviewer. The standard method of the Cochrane Collaboration described in the Cochrane Collaboration Handbook was used to perform this systematic review. Data extraction was performed independently by each reviewer, with differences being resolved by discussion. The following outcomes were determined: mortality in the neonatal period, long term neurodevelopmental outcome, radiological evidence of severe neurological injury, short term haemodynamic changes and incidence of adverse effects. The effect of interventions is expressed either as Relative Risk (RR), Risk Difference (RD) or as Weighted Mean Difference (WMD) with their 95% Confidence Interval (CI). Four trials met the pre-defined criteria for inclusion in this review. There was no evidence of a significant difference between dopamine and dobutamine in terms of neonatal mortality (RD 0.02 95% CI -0.12 to 0.16), incidence of periventricular leukomalacia (RD -0.08, 95% CI -0.19 to 0.04), or severe periventricular haemorrhage (RD -0.02, 95% CI -0.13 to 0.09). Dopamine was more successful than dobutamine in treating systemic hypotension, with fewer infants having treatment failure (RD -0.29, 95% CI -0.42 to -0.17; NNT = 3.5, 95% CI 2.4 to 5.9). There was no evidence of a significant difference in change in left ventricular output when dopamine was compared with dobutamine (WMD -83 ml/kg/min, 95% CI -174 to 8 ml/kg/min). There was no evidence of a significant difference between the two agents with respect to the incidence of tachycardia (RD -0.06, 95% CI -0.25 to 0.14). None of the studies reported the incidence of adverse long term neurodevelopmental outcome. Dopamine is more effective than dobutamine in the short term treatment of systemic hypotension in preterm infants. There was no evidence of an effect on the incidence of adverse neuroradiological sequelae (severe periventricular haemorrhage and/or periventricular leucomalacia), or on the incidence of tachycardia. However, in the absence of data confirming long term benefit and safety of dopamine compared to dobutamine, no firm recommendations can be made regarding the choice of drug to treat hypotension.

Chorioamnionitis and Outcome in Extremely Preterm Infants

Introduction: Chorioamnionitis is a risk factor for preterm delivery. Intrauterine infection leads to the fetal inflammatory response which is characterised by elevated cytokine levels. Chorioamnionitis is reported to cause accelerated but abnormal lung maturation, resulting in decreased incidence of respiratory distress syndrome (RDS) but increased chronic lung disease (CLD), and predisposes the infant to cerebral injury. Objective: To investigate the relation between chorioamnionitis and RDS, CLD, cerebral lesions, neurodevelopmental outcome and mortality in a cohort of extremely premature infants. Materials and Methods: Infants born between 1997 and 2001 with a gestational age of less than 28 weeks or a birth weight of less than 1000 g were divided into two groups: Group 1 with evidence of chorioamnionitis and Group 2 without. Outcomes of these two groups of infants were compared. Results: A total of 388 infants were included (105 in Group 1 and 283 in Group 2). Chorioamnionitis was significantly associated with an increased risk of extreme preterm delivery. Group 1 showed a trend towards an increased incidence of CLD and mortality, while the incidence of periventricular leukomalacia, retinopathy of prematurity (ROP) and necrotising enterocolitis (NEC) were similar between the two groups. Subgroup analysis of 2-year neurodevelopmental outcome showed an increased trend towards cerebral palsy and visual impairment, while the incidence of developmental delay and hearing impairment are similar between the two groups. Conclusion: Extremely preterm infants with chorioamnionitis showed a trend towards an increased incidence of CLD, mortality, cerebral palsy and visual impairment, but a decreased risk of RDS.

POSSIBLE CORRELATION BETWEEN HIGH LEVELS OF IL-18 IN THE CORD BLOOD OF PRE-TERM INFANTS AND NEONATAL DEVELOPMENT OF PERIVENTRICULAR LEUKOMALACIA AND CEREBRAL PALSY

Periventricular leukomalacia (PVL) is a neonatal white matter damage of the brain of pre-term infants that often leads to cerebral palsy (CP). At present, diagnosis of PVL can be done by magnetic resonance imaging (MRI) and ultrasonography only when the infant is at least one week of age. No biochemical methods are available to identify high-risk infants at birth. Cytokines are usually not present in the cord blood but recently an elevation of IL-6 and TNF-α levels has been reported in amniotic fluid, cord blood and brain sections of infants with white matter damages. Levels of interleukin-18 (IL-18), a pleiotropic cytokines expressed in the brain and many other tissues, are highly sensitive to pathophysiological changes to raise the possibility that IL-18 may provide a useful indicator of PVL. The cord blood from 17 pre-term infants with PVL, 38 pre-term infants without PVL, and 30 normal full-term infants were retrospectively analysed for IL-18, IL-6, IL-1β, and TNF-α. The possible factors involved in alteration of IL-18 concentration in relation to PVL and CP were examined. IL-18 is undetectable in the cord blood of normal full-term infants. However, high levels of IL-18 exist in the cord blood samples obtained from pre-term infants who neonatally developed PVL followed by CP. For pre-term infants under 35 weeks of gestation, seven out of eight showing more than 200pg/ml of IL-18 (87.5%) developed PVL neonatally, with five of them subsequently developing CP. In contrast, only five out of 38 pre-term infants with less than 100pg/ml of IL-18 (13.2%) developed PVL. For pre-term infants with less than 30 weeks of gestation, eight out of nine showing more than 100pg/ml of IL-18 (88.9%) developed PVL, with six of these eight (75%) developing CP later. In conclusion, the presence of high levels of IL-18 in the cord blood of the pre-term infants is correlated with the incidence of PVL and CP and may provide a prognostic marker applicable at birth.

Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury

Hypoxic-ischemic injury to the periventricular cerebral white matter [periventricular leukomalacia (PVL)] results in cerebral palsy and is the leading cause of brain injury in premature infants. The principal feature of PVL is a chronic disturbance of myelination and suggests that oligodendrocyte (OL) lineage progression is disrupted by ischemic injury. We determined the OL lineage stages at risk for injury during the developmental window of vulnerability for PVL (23-32 weeks, postconceptional age). In 26 normal control autopsy human brains, OL lineage progression was defined in parietal white matter, a region of predilection for PVL. Three successive OL stages, the late OL progenitor, the immature OL, and the mature OL, were characterized between 18 and 41 weeks with anti-NG2 proteoglycan, O4, O1, and anti-myelin basic protein (anti-MBP) antibodies. NG2+O4+ late OL progenitors were the predominant stage throughout the latter half of gestation. Between 18 and 27 weeks, O4+O1+ immature OLs were a minor population (9.9 +/- 2.1% of total OLs; n = 9). Between 28 and 41 weeks, an increase in immature OLs to 30.9 +/- 2.1% of total OLs (n = 9) was accompanied by a progressive increase in MBP+ myelin sheaths that were restricted to the periventricular white matter. The developmental window of high risk for PVL thus precedes the onset of myelination and identifies the late OL progenitor as the major potential target. Moreover, the decline in incidence of PVL at approximately 32 weeks coincides with the onset of myelination in the periventricular white matter and suggests that the risk for PVL is related to the presence of late OL progenitors in the periventricular white matter.

Antenatal steroids and neonatal periventricular leukomalacia

Objective: To evaluate the effect of antenatal steroid treatment on the development of neonatal periventricular leukomalacia. Methods: This retrospective cohort study included 1161 neonates with gestational ages of 24–34 weeks and birth weights of 500–1750 g, divided into two groups on the basis of antenatal steroid treatment. Neonatal neurosonograms were done on days 3 and 7 of life and labeled normal or abnormal. The abnormal outcomes evaluated were periventricular leukomalacia or intraventricular hemorrhage, periventricular leukomalacia with intraventricular hemorrhage, and isolated periventricular leukomalacia. The group treated with antenatal steroids was compared with the untreated group for these outcomes. Results: Antenatal steroids were associated with significantly less periventricular leukomalacia or intraventricular hemorrhage (23% versus 31%, P = .005), periventricular leukomalacia with intraventricular hemorrhage (5% versus 11%, P = .001), and isolated periventricular leukomalacia (3% versus 7%, P = .009). Logistic regression analysis of antenatal steroid treatment, controlling for confounding maternal and neonatal characteristics, indicated that neonates treated with antenatal steroids had a 56% lower likelihood of periventricular leukomalacia with intraventricular hemorrhage (adjusted odds ratio [OR] 0.44, 95% confidence interval [CI] 0.25, 0.77) and a 58% lower likelihood of isolated periventricular leukomalacia (adjusted OR 0.42, 95% CI 0.20, 0.88). Conclusion: Antenatal steroid treatment was associated with over 50% reduction in the incidence of periventricular leukomalacia in preterm neonates. Increased use of antenatal steroid therapy might improve long-term neonatal neurologic outcomes.